ªÂÙ·‚ÔÏÈο
ÓÔÛ‹Ì·Ù· Û ·È‰È¿ Î·È Ó¤Ô˘˜. ¶ÚÒÙË ÈÏÔÙÈ΋ ÌÂϤÙË ÛÙËÓ ∫Ú‹ÙË
∂. ªÈ¯·ËÏ›‰Ô˘1, Ã. §ÈÔÓ‹˜3, ª. ™ËÏÈÒÙË2, ¶. ¶·Û·Ï¿ÎË1, ¶. ¡ÈÎËÙ¿Î˘3, ∂. ¶··‰ÔÔ‡ÏÔ˘1, ¡. ∫·Ù˙ËÏ¿Î˘1, Œ. ∆Û·¿ÎË1, ∏. ª·ÓÈ·‰¿ÎË1, ¶. µÔÚÁÈ¿1, ∞. ∫·ÓÈÙÛ¿Î˘4, ∂. ∫fiÎÔÚË5, R. A. Wevers6, ™. ™Ì˘Ú¿ÎȘ1, ∞. ∂˘·ÁÁÂÏ›Ô˘2
Inherited metabolic disorders in children and young adults. First pilot study in Crete H. Michailidou1, C. Lionis3, M. Spilioti2, P. Paspalaki1, P. Nikitakis3, E. Papadopoulou1, N. Katzilakis1, E. Tsapaki1, H. Maniadaki1, P. Vorgia1, A. Kanitsakis4, E. Kokori5, R. A. Wevers6, S. Sbyrakis1, A. Evangeliou2
¶ÂÚ›ÏË„Ë: T· ÂÓ‰ÔÁÂÓ‹ ÌÂÙ·‚ÔÏÈο ÓÔÛ‹Ì·Ù·
˘Ô‰È·ÁÈÁÓÒÛÎÔÓÙ·È. O ÛÎÔfi˜ Ù˘ ÈÏÔÙÈ΋˜ ·˘Ù‹˜ ÌÂϤÙ˘ Â›Ó·È Ó· ·ÚÔ˘ÛÈ¿ÛÂÈ Ù· ÚÒÙ· ·ÔÙÂϤÛÌ·Ù· Î·È ÙËÓ ÂÌÂÈÚ›· Ô˘ ·ÔÎÙ‹ıËΠ·fi ÙË Û˘ÓÂÚÁ·Û›· È·ÙÚÒÓ Ô˘ ÂÚÁ¿˙ÔÓÙ·È ÛÙËÓ ÚˆÙÔ‚¿ıÌÈ· ÊÚÔÓÙ›‰· ˘Á›·˜ Û ·ÁÚÔÙÈΤ˜ ÂÚÈÔ¯¤˜ Ù˘ ∫Ú‹Ù˘ Ì ¤Ó· ÂÍÂȉÈÎÂ˘Ì¤ÓÔ ·ÓÂÈÛÙËÌÈ·Îfi ΤÓÙÚÔ. OÈ ÁÈ·ÙÚÔ› Ô˘ ÂÚÁ¿˙ÔÓÙ·È Û 8 ΤÓÙÚ· ˘Á›·˜ ÛÙËÓ ·ÁÚÔÙÈ΋ ÂÚÈÔ¯‹ Ù˘ ∫Ú‹Ù˘ (·È‰›·ÙÚÔÈ Î·È ÁÂÓÈÎÔ› È·ÙÚÔ›) ·Ú¤ÂÌ„·Ó 112 ·ÛıÂÓ›˜ Ô˘ ÏËÚÔ‡Û·Ó ¤Ó· ÙÔ˘Ï¿¯ÈÛÙÔÓ ·fi Ù·
ÎÚÈÙ‹ÚÈ· (Û˘ÌÙÒÌ·Ù· ‹ ¯·Ú·ÎÙËÚÈÛÙÈο) ÂÓfi˜
ÂÚˆÙËÌ·ÙÔÏÔÁ›Ô˘ Ô˘ ÙÔ˘˜ ›¯Â ‰È·ÓÂÌËı›, ÛÙÔ
¶·ÓÂÈÛÙËÌÈ·Îfi ¡ÔÛÔÎÔÌÂ›Ô ∏Ú·ÎÏ›Ԣ, Ì ÙËÓ ˘Ô„›· ÂÓ‰ÔÁÂÓÔ‡˜ ÌÂÙ·‚ÔÏÈÎÔ‡ ÓÔÛ‹Ì·ÙÔ˜. ªÂÙ¿ ·fi ÂÍÂȉÈÎÂ˘Ì¤ÓÔ ÎÏÈÓÈÎfi, ÂÚÁ·ÛÙËÚÈ·Îfi Î·È ·ÂÈÎÔÓÈÛÙÈÎfi ¤ÏÂÁ¯Ô Û 17/112 ·ÛıÂÓ›˜ (15,2%) ÂȂ‚·ÈÒıËÎÂ Ë ‰È¿ÁÓˆÛË ÌÂÙ·‚ÔÏÈÎÔ‡ ÓÔÛ‹Ì·ÙÔ˜.
¢Âη٤ÛÛÂÚȘ ·fi ÙÔ˘˜ 17 ·ÛıÂÓ›˜ ‹Ù·Ó ·È‰È¿. ™ÙÔ˘˜ ·ÛıÂÓ›˜ ÂÊ·ÚÌfiÛÙËÎÂ, fiÔ˘ ‹Ù·Ó ‰˘Ó·Ùfi, Ë Î·Ù¿ÏÏËÏË ıÂڷ¢ÙÈ΋ ·ÓÙÈÌÂÙÒÈÛË, ÂÓÒ
ÛÙÔ˘˜ ›‰ÈÔ˘˜ Î·È ÙȘ ÔÈÎÔÁ¤ÓÂȤ˜ ÙÔ˘˜ ·Ú·Û¯¤ıËΠοı ‰˘Ó·Ù‹ ÎÔÈÓˆÓÈÎÔÔÈÎÔÓÔÌÈ΋ ˘ÔÛÙ‹ÚÈÍË. ¶·Ú¿ÏÏËÏ·, ¤ÁÈÓ ÁÂÓÂÙÈ΋ ηıÔ‰‹ÁËÛË Î·È Û˘Ì‚Ô˘Ï¢ÙÈ΋ Ù˘ ÔÈÎÔÁ¤ÓÂÈ·˜ ÙˆÓ ·Û¯fiÓÙˆÓ. ∏ Û˘Ì‚ÔÏ‹ ÙˆÓ ÁÈ·ÙÚÒÓ Ù˘ ÚˆÙÔ‚¿ıÌÈ·˜ ÊÚÔÓÙ›‰·˜ ˘Á›·˜ ÛÙËÓ ¤ÁηÈÚË ‰È¿ÁÓˆÛË ÙˆÓ ÌÂÙ·‚ÔÏÈÎÒÓ ÓÔÛËÌ¿ÙˆÓ ÛÙ· ·È‰È¿ Ê·›ÓÂÙ·È Ó· Â›Ó·È ÛËÌ·-
1 ¶·È‰È·ÙÚÈ΋
¡ÔÛÔÎÔÌÂ›Ô ∏Ú·ÎÏ›Ԣ (¶∂¶∞°¡∏), ∫Ú‹ÙË
2 ¡Â˘ÚÔÏÔÁÈ΋ ∫ÏÈÓÈ΋, ¶∂¶∞°¡∏, ∫Ú‹ÙË
3 ∆Ô̤·˜ ∫ÔÈÓˆÓÈ΋˜ π·ÙÚÈ΋˜, ¶∂¶∞°¡∏, ∫Ú‹ÙË
Abstract: Inherited metabolic disorders are often underdiagnosed. The aim of this pilot study is to present the main outcomes and the experience gained as a result of the cooperation between the medical staff of the primary health care system in the rural areas of Crete and the tertiary care doctors at the referral University Hospital of Heraklion, Crete. Medical staff working in 8 primary health care centers in rural Crete (pediatricians and general practitioners) referred 112 patients suspected for metabolic disease who fulfilled at least 1 criterion (symptom or sign) from a pre-constructed questionnaire. After detailed clinical and laboratory investigations 17 of 112 patients (15.2 %) were found to have an inherited metabolic disease. Fourteen of these patients were children. Where possible, these patients were provided with the appropriate treatment. Additionally,socio-economical support and genetic consultation was made available to all of them and their families. A high index of suspicion, proper training and supply of information to the primary health care physicians may contribute to the timely detection of patients with inherited metabolic diseasesand the prevention and treatment of new cases.
°ÂÓÈÎfi
4 ¶·È‰È·ÙÚÈ΋ ∫ÏÈÓÈ΋, °ÂÓÈÎfi ¡ÔÛÔÎÔÌÂ›Ô Ã·Ó›ˆÓ, ∫Ú‹ÙË
5 ¶·È‰È·ÙÚÈ΋ ∫ÏÈÓÈ΋, µÂÓÈ˙¤ÏÂÈÔ °ÂÓÈÎfi ¡ÔÛÔÎÔÌÂ›Ô ∏Ú·ÎÏ›Ԣ, ∫Ú‹ÙË
6 University Hospital Nigmegen, The Netherlands Department of Neurology and Pediatrics
1 Department of Pediatrics, Medical School, University of Heraklion, Crete
2 Department of Neurology, Medical School, University of Heraklion, Crete
3 Department of Public Health and Social Medicine, Medical School, University of Heraklion, Crete
4 Pediatric Clinic, General Hospital of Chania, Crete
5 Department of Pediatrics, Venizelio General Hospital of Heraklion, Crete
6 University Hospital Nigmegen, The Netherlands Department of Neurology and Pediatrics
ÂÓË̤ڈÛË ÌÔÚÔ‡Ó Ó· ·ÓȯÓÂ‡Ô˘Ó ¤ÁηÈÚ· ·ÛıÂÓ›˜ Ì ˘fiÓÔÈ· ÌÂÙ·‚ÔÏÈÎÔ‡ ÓÔÛ‹Ì·ÙÔ˜ Î·È Ó· η-
Ù¢ı‡ÓÔ˘Ó ÛÙË ÛˆÛÙ‹ ÚÔÏËÙÈ΋ Î·È ıÂڷ¢ÙÈ΋
·ÓÙÈÌÂÙÒÈÛË ÙˆÓ ÓÔÛËÌ¿ÙˆÓ ·˘ÙÒÓ.
§¤ÍÂȘ ÎÏÂȉȿ: ÂÓ‰ÔÁÂÓ‹ ÌÂÙ·‚ÔÏÈο ÓÔÛ‹Ì·Ù·,
ÚˆÙÔ‚¿ıÌÈ· ÊÚÔÓÙ›‰· ˘Á›·˜.
∂ÈÛ·ÁˆÁ‹
OÈ ÂÓ‰ÔÁÂÓ›˜ ‰È·Ù·Ú·¯¤˜ ÙÔ˘ ÌÂÙ·‚ÔÏÈÛÌÔ‡
‰ÂÓ Â›Ó·È ÙfiÛÔ Û¿ÓȘ fiÛÔ ÈÛÙ¢fiÙ·Ó ÚÈÓ ÌÂÚÈο
¯ÚfiÓÈ· (1-4). ªÂ ÙËÓ ·Ó¿Ù˘ÍË Ù˘ Ù¯ÓÔÏÔÁ›·˜ ηÈ
Ù˘ ¤Ú¢ӷ˜ fiÏÔ Î·È ÈÔ Û˘¯Ó¿ ‰È·ÁÈÁÓÒÛÎÔÓÙ·È
ÌÂÙ·‚ÔÏÈο ÓÔÛ‹Ì·Ù·, ÌÂÚÈο ·fi Ù· ÔÔ›· ÁÈ·
ÚÒÙË ÊÔÚ¿, Ì ·ÔÙ¤ÏÂÛÌ· ÙËÓ ¤ÁηÈÚË, Û˘¯Ó¿, ¤Ó·ÚÍË ·ÔÙÂÏÂÛÌ·ÙÈ΋˜ ıÂڷ¢ÙÈ΋˜ ·ÁˆÁ‹˜
Î·È ÚÔÏËÙÈ΋˜ ·ÓÙÈÌÂÙÒÈÛ˘ (5,6).
∏ ÌÂϤÙË ÙˆÓ ÂÓ‰ÔÁÂÓÒÓ ÌÂÙ·‚ÔÏÈÎÒÓ ÓÔÛËÌ¿-
ÙˆÓ (∂ª¡) ÛÙËÓ ∫Ú‹ÙË, ¤Ó· ÓËÛ› Ì ÏËı˘ÛÌfi ÌÂ-
Á·Ï‡ÙÂÚÔ ·fi 500.000 ηÙÔ›ÎÔ˘˜, ·ÔÎÙ¿ ȉȷ›ÙÂ-
ÚÔ ÂӉȷʤÚÔÓ Î·ıÒ˜: ·) ∏ ÏÂÈÔ„ËÊ›· ÙˆÓ ÁÈ·ÙÚÒÓ Ô˘ ÂÚÁ¿˙ÔÓÙ·Ó
ÛÙ· ΤÓÙÚ· ˘Á›·˜ ̤¯ÚÈ ÚfiÛÊ·Ù· ‹Ù·Ó ·ÓÂȉ›Î¢ÙÔÈ Ô˘ ÂÎÏ‹ÚˆÓ·Ó ÙËÓ ˘Ô¯ÚˆÙÈ΋ ıËÙ›·
¯ˆÚ›˜ ÙËÓ Î·Ù¿ÏÏËÏË Âη›‰Â˘ÛË Î·È
ÒÛÙ ӷ ·Ó·ÁÓˆÚ›˙Ô˘Ó ¤ÁηÈÚ· ÙȘ ÎÏÈÓÈ-
Τ˜ ÂΉËÏÒÛÂȘ ÙˆÓ Ó¢ÚÔÌÂÙ·‚ÔÏÈÎÒÓ ÓÔÛËÌ¿-
ÙˆÓ. ™ÙÔ˘˜ ÁÈ·ÙÚÔ‡˜ ·˘ÙÔ‡˜ ‰ÂÓ ‹Ù·Ó ÚÔÛÈÙ‹ Ë ‚È-
‚ÏÈÔÁÚ·Ê›· ÁÈ· ÙȘ ÚfiÛÊ·Ù˜ ÂÍÂÏ›ÍÂȘ Î·È ‰˘Ó·-
ÙfiÙËÙ˜ Ù˘ ÌÔÚȷ΋˜ ‚ÈÔÏÔÁ›·˜ Î·È ‚ÈÔ¯ËÌ›·˜
ÛÙË ‰È¿ÁÓˆÛË ÙˆÓ Ó¢ÚÔÌÂÙ·‚ÔÏÈÎÒÓ ÓÔÛËÌ¿ÙˆÓ
ÛÙËÓ ∂ÏÏ¿‰· Î·È ÙÔ Â͈ÙÂÚÈÎfi. ‚) ™ÙȘ ·ÔÌÔӈ̤Ó˜ ·ÁÚÔÙÈΤ˜ ÂÚÈÔ¯¤˜ Ù˘
∫Ú‹Ù˘, fiÔ˘ Ê·›ÓÂÙ·È fiÙÈ ÂÓÙÔ›˙ÂÙ·È Ë ÏÂÈÔÓfiÙËÙ· ÙˆÓ ·‰È¿ÁÓˆÛÙˆÓ ÌÂÙ·‚ÔÏÈÎÒÓ ÓÔÛËÌ¿ÙˆÓ, ˘¿Ú¯Ô˘Ó ȉȷ›ÙÂÚ˜ ÎÔÈÓˆÓÈΤ˜ Î·È ÔÏÈÙÈÛÌÈΤ˜
Û˘Óı‹Î˜, οÙÈ Ô˘ Â›Ó·È Èı·Ófi Ó· ηıÈÛÙ¿ ÙËÓ
·ʋ Ì ÙÔÓ È·ÙÚfi ‰‡ÛÎÔÏË. Á) ∆Ô ¶·ÓÂÈÛÙËÌÈ·Îfi ¡ÔÛÔÎÔÌÂ›Ô Ù˘ ∫Ú‹Ù˘
ÛÙÔ ∏Ú¿ÎÏÂÈÔ, ÙÔ ÔÔ›Ô ‚Ú›ÛÎÂÙ·È ÛÙÔ Ì¤ÛÔ Ù˘ Ó‹-
ÛÔ˘, ÏÂÈÙÔ˘ÚÁ› Â‰Ò Î·È 12 ¯ÚfiÓÈ·. ŸÌˆ˜, Ù· ÙÂ-
ÏÂ˘Ù·›· ¯ÚfiÓÈ· ¤ÁÈÓ ȉȷ›ÙÂÚË ÚÔÛ¿ıÂÈ· ÁÈ· ÙËÓ
·Ó¿Ù˘ÍË Ù˘ ÌÔÓ¿‰·˜ ÌÂÙ·‚ÔÏÈÎÒÓ ÓÔÛËÌ¿ÙˆÓ
ÛÙËÓ ¶·È‰È·ÙÚÈ΋ ∫ÏÈÓÈ΋. øÛÙfiÛÔ, ÚԤ΢„·Ó ·Ú-
ÎÂÙ¤˜ ‰˘ÛÎÔϛ˜ ÁÈ·Ù› ÂÎÙfi˜ ·fi ÙËÓ ·Ó·Ú΋ ÂÓË̤ڈÛË ÙˆÓ ÁÈ·ÙÚÒÓ Ù˘ ÚˆÙÔ‚¿ıÌÈ·˜ ÊÚÔÓÙ›‰·˜ ˘Á›·˜ (¶ºÀ), ˘¿Ú¯Ô˘Ó
Key words: inherited metabolic diseases, primary health care
fiÔ˘ ÙÔ ÙÌ‹Ì· π·ÙÚÈ΋˜ ÙÔ˘
ÓÔÛËÌ¿ÙˆÓ ÛÙËÓ ∫Ú‹ÙË. ∏ ‰ÈÂÚ‡ÓËÛË ÙÔ˘ ÚfiÏÔ˘ Î·È Ù˘ Û˘Ì‚ÔÏ‹˜ ÙˆÓ ÁÈ·ÙÚÒÓ Ù˘
ÛÙËÓ ·Ó›¯Ó¢ÛË Î·È Î·ıÔ‰‹ÁËÛË ·ÙfiÌˆÓ ÌÂ
ÌÂÙ·‚ÔÏÈÎÔ‡ ÓÔÛ‹Ì·ÙÔ˜ ÛÙȘ ‰˘ÛÚfiÛÈÙ˜ ·ÁÚÔÙÈΤ˜ ÂÚÈÔ¯¤˜ Ù˘ ∫Ú‹Ù˘ ·ÔÙÂÏ› ¤Ó· ÂÍ·ÈÚÂÙÈο ÂӉȷʤÚÔÓ ÎÏÈÓÈÎfi ı¤Ì·. °È· ÙÔ ÛÎÔfi ·˘Ùfi Û˘ÓÂÚÁ¿ÛÙËÎ·Ó ÔÈ ¶·È‰È·ÙÚÈΤ˜ ∫ÏÈÓÈΤ˜ ÙÔ˘ ¶·ÓÂÈÛÙËÌ›Ô˘ ∫Ú‹Ù˘, ÙÔ˘ µÂÓÈ˙¤ÏÂÈÔ˘ ¡ÔÛÔÎÔÌ›Ԣ Î·È ÙˆÓ Ã·Ó›ˆÓ, Ë ¡Â˘ÚÔÏÔÁÈ΋ ∫ÏÈÓÈ΋ Î·È Ô ∆Ô̤·˜ ∫ÔÈÓˆÓÈ΋˜ π·ÙÚÈ΋˜ ÙÔ˘ ¶·ÓÂÈÛÙËÌ›Ô˘ ∫Ú‹Ù˘ Ì 8 ΤÓÙÚ· ˘Á›·˜ ÛÙȘ ·ÁÚÔÙÈΤ˜ ÂÚÈÔ¯¤˜ Ù˘ ∫Ú‹Ù˘. O ÛÎÔfi˜ ·˘Ù‹˜ Ù˘ ÈÏÔÙÈ΋˜ ÌÂϤÙ˘ Â›Ó·È Ó· ·ÚÔ˘ÛÈ¿ÛÂÈ Ù· ÚÒÙ· ·ÔÙÂϤÛÌ·Ù· Î·È ÙËÓ ÂÌÂÈÚ›· ·fi ·˘Ù‹ ÙË Û˘ÓÂÚÁ·Û›· Î·È Ó· Û˘˙ËÙ‹ÛÂÈ ÙË Û˘Ì‚ÔÏ‹ ÙˆÓ ÁÈ·ÙÚÒÓ Ô˘ ÂÚÁ¿˙ÔÓÙ·È ÛÙË ÚˆÙÔ‚¿ıÌÈ· ÊÚÔÓÙ›‰· ˘Á›·˜ ÛÙË ‰È¿ÁÓˆÛË Î·È ·ÓÙÈÌÂÙÒÈÛË ÙˆÓ ·ÛıÂÓÒÓ Ì ÂÓ‰ÔÁÂÓ‹ ÌÂÙ·‚ÔÏÈο ÓÔÛ‹Ì·Ù·.
ÀÏÈÎfi Î·È Ì¤ıÔ‰ÔÈ ∏ ÌÂϤÙË ‰ÈÂÍ‹¯ıË Î·Ù¿ ÙÔ ¯ÚÔÓÈÎfi ‰È¿ÛÙËÌ· 1997-1999 ÛÙËÓ ·ÁÚÔÙÈ΋ ÂÚÈʤÚÂÈ· Ù˘ ∫Ú‹Ù˘. ™˘ÌÂÚÈÏ‹ÊıËÎ·Ó 8 ΤÓÙÚ· ÚˆÙÔ‚¿ıÌÈ·˜ ÊÚÔÓÙ›‰·˜ ˘Á›·˜ ÛÙÔ ÓËÛ› (™‹ÏÈ, ¶¤Ú·Ì·, ∞ÓÒÁÂÈ·, ∫¿ÓÙ·ÓÔ˜, ∫·ÛÙ¤ÏÏÈ, ªÔ›Ú˜, ∞Ú¯¿Ó˜ Î·È ¡Â¿ÔÏȘ) (∂ÈÎfiÓ· 1).
OÎÙÒ ÂȉÈÎÂ˘Ì¤ÓÔÈ È·ÙÚÔ› ÙˆÓ Î¤ÓÙÚˆÓ ·˘ÙÒÓ (4 ÁÂÓÈÎÔ› È·ÙÚÔ›, 4 ·È‰›·ÙÚÔÈ) ÂÎÏ‹ıËÛ·Ó Î·È Û˘ÌÌÂÙ›¯·Ó Û ÂÎ·È‰Â˘ÙÈΤ˜ ÚÔηٷÚÎÙÈΤ˜ Û˘Ó·ÓÙ‹ÛÂȘ ÛÙÔ ¶·ÓÂÈÛÙ‹ÌÈÔ ∫Ú‹Ù˘. ¶ÚÈÓ ÙËÓ ÂÊ·ÚÌÔÁ‹ ÙÔ˘ ÚÔÁÚ¿ÌÌ·ÙÔ˜, ηıÔÚ›ÛÙËΠ¤Ó·˜ ηٿÏÔÁÔ˜ Ì ÎÚÈÙ‹ÚÈ· ÂÈÛ·ÁˆÁ‹˜ ·ÛıÂÓÒÓ ÛÙË ÌÂϤÙË Ô˘ ‚·Û›ÛÙËΠ۠ÂȉÈο ‹ ÌË ÂȉÈο
¤¯ÂÈ Î·ıÈÂÚÒÛÂÈ Âη›‰Â˘ÛË Î·È Ú·ÎÙÈ΋ ¿ÛÎËÛË ÛÙËÓ ¶ºÀ, ÏÂÈÙÔ˘ÚÁ› Ù· ÙÂÏÂ˘Ù·›· ¯ÚfiÓÈ· ¤Ó· ‰›ÎÙ˘Ô ˆ˜ ·ÔÙ¤ÏÂÛÌ· Ù˘ Û˘ÓÂÚÁ·Û›·˜ ÙÔ˘ ∆Ô̤· ∫ÔÈÓˆÓÈ΋˜ π·ÙÚÈ΋˜ Î·È 10 ΤÓÙÚˆÓ ˘Á›·˜. ∂ÈϤÔÓ, Â›Ó·È È‰È·›ÙÂÚ· ÛËÌ·ÓÙÈÎfi ÙÔ ÁÂÁÔÓfi˜ fiÙÈ ÌÂÙ¿ ÙÔ 1995 ÂÎÙfi˜ ·fi ÙÔ˘˜ ÂȉÈÎÂ˘Ì¤ÓÔ˘˜ ÁÂÓÈÎÔ‡˜ È·ÙÚÔ‡˜, ÂȉÈÎÂ˘Ì¤ÓÔÈ ·È‰›·ÙÚÔÈ ÛÙÂϯÒÓÔ˘Ó Ù· ÂÚÈÛÛfiÙÂÚ· ΤÓÙÚ· ˘Á›·˜ ÛÙËÓ ∫Ú‹ÙË. ™ËÌ·ÓÙÈ΋, ›Û˘, Ù· ÙÂÏÂ˘Ù·›· ¯ÚfiÓÈ· ‹Ù·Ó Î·È Ë ÚÔÛ¿ıÂÈ· Û˘ÓÂÚÁ·Û›·˜ ÌÂٷ͇ Ù˘ ∫ÏÈÓÈ΋˜ ∫ÔÈÓˆÓÈ΋˜ π·ÙÚÈ΋˜ ÙÔ˘ ¶·ÓÂÈÛÙËÌ›Ô˘ ∫Ú‹Ù˘ Î·È Ù˘ ªÔÓ¿‰·˜ ªÂÙ·‚ÔÏÈÎÒÓ ¡fiÛˆÓ Ù˘ ¶·È‰È·ÙÚÈ΋˜ ∫ÏÈÓÈ΋˜ ÙÔ˘ ¶·ÓÂÈÛÙËÌÈ·ÎÔ‡ °ÂÓÈÎÔ‡ ¡ÔÛÔÎÔÌ›Ԣ
Û˘ÌÙÒÌ·Ù· Ô˘ Û˘¯Ó¿ ·Ú·ÙËÚÔ‡ÓÙ·È Û ·ÛıÂÓ›˜ Ì ÌÂÙ·‚ÔÏÈο ÓÔÛ‹Ì·Ù· (7-9). O ηٿÏÔÁÔ˜ Ì ٷ ÎÚÈÙ‹ÚÈ·, Û‡Ìʈӷ Ì ٷ ÔÔ›· ÔÈ ·ÛıÂÓ›˜ ·Ú·¤ÌÊıËÎ·Ó Ì ÙËÓ ˘fiÓÔÈ· ÌÂÙ·‚ÔÏÈÎÔ‡ ÓÔÛ‹Ì·ÙÔ˜ ÛÙÔ ¶·ÓÂÈÛÙËÌÈ·Îfi ¡ÔÛÔÎÔ-
ÌÂ›Ô ∏Ú·ÎÏ›Ԣ, Ê·›ÓÂÙ·È ÛÙÔÓ ¶›Ó·Î· 1. OÈ ÁÈ·ÙÚÔ› Ù˘ ÚˆÙÔ‚¿ıÌÈ·˜ ÊÚÔÓÙ›‰·˜ ˘Á›·˜ ¤ÏÂÁ¯·Ó ÙËÓ ·ÚÔ˘Û›· ÙˆÓ ÎÚÈÙËÚ›ˆÓ ·˘ÙÒÓ ÛÙÔ˘˜ ·ÛıÂÓ›˜ ÙÔ˘˜ Î·È ·Ú¤ÂÌ·Ó ·ÛıÂÓ›˜
Ì 1 ‹ ÂÚÈÛÛfiÙÂÚ· ÎÚÈÙ‹ÚÈ· ÛÙË ÌÔÓ¿‰· ÂÓ‰ÔÁÂÓÒÓ ÓÔÛËÌ¿ÙˆÓ ÙÔ˘ ÌÂÙ·‚ÔÏÈÛÌÔ‡ Ù˘ ¶·È‰È·ÙÚÈ΋˜ ∫ÏÈÓÈ΋˜ ÙÔ˘ ¶·ÓÂÈÛÙËÌ›Ô˘ ∫Ú‹Ù˘, Ë ÔÔ›· ÏÂÈÙÔ˘ÚÁ› ÛÙÔ ¶·°¡∏. ∞ÎÔÏÔ‡ıˆ˜, ÔÈ È·ÙÚÔ› Ù˘ ÌÔÓ¿‰·˜, ÛÂ Û˘ÓÂÚÁ·Û›· Ì ÙË
¡Â˘ÚÔÏÔÁÈ΋ ∫ÏÈÓÈ΋ ÙÔ˘ ›‰ÈÔ˘ ¡ÔÛÔÎÔÌ›Ԣ, ÂÊ¿ÚÌÔ˙·Ó ÏÂ-
ÙÔÌÂÚ‹ ÎÏÈÓÈ΋ Ó¢ÚÔÏÔÁÈ΋ ÂͤٷÛË ÛÙÔ˘˜ ·ÛıÂÓ›˜ Ô˘
·Ú·¤ÌÊıËÎ·Ó Î·È ·Ó¿ÏÔÁ· ÚÔ¯ˆÚÔ‡Û·Ó Û ÂÍÂȉÈÎÂ˘Ì¤-
ÓÔ ÂÚÁ·ÛÙËÚÈ·Îfi ¤ÏÂÁ¯Ô. O ÂÚÁ·ÛÙËÚÈ·Îfi˜ ¤ÏÂÁ¯Ô˜ Ô˘
·ÎÔÏÔ‡ıËÛ ÛÙËÚ›¯ıËΠÛÙËÓ ÎÏÈÓÈ΋ Û˘Ìو̷ÙÔÏÔÁ›·, ÛÙÔ
ÈÛÙÔÚÈÎfi Î·È ÙËÓ ÂȉÈ΋ ηÙ‡ı˘ÓÛË Ô˘ ‰fiıËΠ̠‚¿ÛË ÙȘ Èı·Ó¤˜ ‰È·ÁÓÒÛÂȘ Ô˘ ηıÔÚ›ÛÙËÎ·Ó ·fi ·È‰ÔÓ¢ÚÔÏfiÁÔ. ™Â fiÏÔ˘˜ ÙÔ˘˜ ·ÛıÂÓ›˜ ¤ÁÈÓ ·Ó¿Ï˘ÛË ·›Ì·ÙÔ˜ (ÁÂÓÈ΋ ÂͤٷÛË ·›Ì·ÙÔ˜ Î·È ÚÔÛ‰ÈÔÚÈÛÌfi˜: ËÏÂÎÙÚÔÏ˘ÙÒÓ, ÙÚ·ÓÛ·ÌÈÓ·ÛÒÓ, ÁÏ˘Îfi˙˘, ·ÂÚ›ˆÓ ·›Ì·ÙÔ˜, ÎÚ·ÙÈÓ›Ó˘, Ô˘Ú›·˜, Ô˘ÚÈÎÔ‡ ÔͤԘ, ÎÚ·ÙÈÓÔʈÛÊÔÎÈÓ¿Û˘ (CPK), ·ÏηÏÈ΋˜ ʈÛÊ·Ù¿Û˘, Á·Ï·ÎÙÈ΋˜ ‰Â¸‰ÚÔÁÂÓ¿Û˘ (LDH), ÙÚÈÁÏ˘ÎÂÚȉ›ˆÓ, ¯ÔÏËÛÙÂÚfiÏ˘, Ì˘ÔÛÊ·ÈÚ›Ó˘, ÊÂÚÈÙÙ›Ó˘).
∞Ó¿ÏÔÁ· Ì ÙËÓ ÎÏÈÓÈ΋ ÂÈÎfiÓ· Î·È È‰È·›ÙÂÚ· › ˘Ô„›·˜ ÌÈÙÔ¯ÔÓ‰ÚÈÔ¿ıÂÈ·˜, ÔÚÁ·ÓÈ΋˜ Ô͢Ԣڛ·˜ ‹ ·ÌÈÓÔÍÂÔ¿ıÂÈ·˜, ¤ÁÈÓ·Ó ÌÂÙÚ‹ÛÂȘ Á·Ï·ÎÙÈÎÔ‡ ÔͤԘ, ˘ÚÔÛÙ·Ê˘ÏÈÎÔ‡ ÔͤԘ, ·ÎÂÙ˘Ï·ÎÂÙÔÍÈÎÔ‡, ‚-O∏ ‚Ô˘Ù˘ÚÈÎÔ‡ ÔͤԘ, ·Ì̈ӛ·˜ Î·È Î·ÚÓÈÙ›Ó˘.
∂ÈϤÔÓ, ¤ÁÈÓ ËÏÂÎÙÚÔÂÁÎÂÊ·ÏÔÁÚ¿ÊËÌ· (∏∂°), ·ÍÔÓÈ΋ ÙÔÌÔÁÚ·Ê›· ÂÁÎÂÊ¿ÏÔ˘ (CT scan) ηÈ, fiÔ˘ ÎÚ›ıËΠÛÎfiÈÌÔ, Ì·ÁÓËÙÈ΋ ÙÔÌÔÁÚ·Ê›· ÂÁÎÂÊ¿ÏÔ˘ (MRI). ∂›Û˘, ÂϤÁ¯ıËÎ·Ó Ù· Ô‡Ú· ÙˆÓ ·ÛıÂÓÒÓ (‚ÈÔ¯ËÌÈ΋, ÌÈÎÚÔÛÎÔÈ΋ ·Ó¿Ï˘ÛË, ¯ÚÒÌ·, ÔÛÌ‹, FeCl3 test, ·Ó·ÁˆÁÈΤ˜ Ô˘Û›Â˜). ªÂ ‚¿ÛË Ù· ·ÔÙÂϤÛÌ·Ù· ·fi ÙÔÓ ·Ú¯ÈÎfi ÂÚÁ·ÛÙËÚÈ·Îfi Î·È ·ÂÈÎÔÓÈÛÙÈÎfi ¤ÏÂÁ¯Ô ¤ÁÈÓ ¤ÏÂÁ¯Ô˜ ÁÈ· ÔÚÁ·ÓÈΤ˜ ÔÍÂÔ˘Ú›Â˜ (·Ó¿Ï˘ÛË ÔÚÁ·ÓÈÎÒÓ ÔͤˆÓ Ô‡ÚˆÓ Ì GC/MS), ÚÔÛ‰ÈÔÚÈÛÌfi˜ ·ÌÈÓÔͤˆÓ ÛÙÔ Ï¿ÛÌ· Î·È Ù· Ô‡Ú·, ÂÓÒ Û ÔÚÈṲ̂Ó˜ ÂÚÈÙÒÛÂȘ Ú·ÁÌ·ÙÔÔÈ‹ıËΠ·Ó¿Ï˘ÛË VLCFA (very long chain fatty acids) ÛÙÔÓ ÔÚfi. ™Â ÂÈÏÂÁ̤Ó˜ ÂÚÈÙÒÛÂȘ ¤ÁÈÓ ÊfiÚ-
ÙÈÛË Ì ÁÏ˘Îfi˙Ë, ÊÚÔ˘ÎÙfi˙Ë, Ê·ÈÓ˘ÏÚÔÈÔÓÈÎfi Ô͇ Î·È Ï‡Έ̷. ∂ÎÙfi˜ ·fi ÙÔÓ ÂȉÈÎfi ÂÚÁ·ÛÙËÚÈ·Îfi Î·È ·ÂÈÎÔÓÈÛÙÈÎfi
¤ÏÂÁ¯Ô, ¤ÁÈÓ·Ó ÂÈÏÂÎÙÈο ÂÚÈÛÛfiÙÂÚÔ ÂÍÂȉÈÎÂ˘Ì¤Ó˜ ÂÍÂÙ¿ÛÂȘ ÚÔÎÂÈ̤ÓÔ˘ Ó· ÙÂı› ÔÚÈÛÙÈο Ë ‰È¿ÁÓˆÛË, fiˆ˜ ÚÔÛ‰ÈÔÚÈÛÌfi˜ ÂÓ˙‡ÌˆÓ Û ‰È¿ÊÔÚÔ˘˜ ÈÛÙÔ‡˜ Î·È ‚ÈÔÏÔÁÈο ˘ÁÚ¿ (·›Ì·, ÈÓÔ‚Ï¿ÛÙ˜, ̇˜, ‹·Ú), fiˆ˜ ›Û˘ ·Ó¿Ï˘ÛË ÁÂÓÂÙÈÎÔ‡ ˘ÏÈÎÔ‡ Û ·ÙÙ·Ú· ·›Ì·ÙÔ˜ Î·È Ì˘˚ο ·ÙÙ·Ú· ÁÈ· ·Ó›-
¯Ó¢ÛË ÁÓˆÛÙÒÓ ÌÂÙ·ÏÏ¿ÍÂˆÓ Û ˘ÚËÓÈÎfi ‹ ÌÈÙÔ¯ÔÓ‰ÚÈ·Îfi
˘ÏÈÎfi. ∏ ‚Ô‹ıÂÈ· ÂȉÈÎÒÓ ·È‰È·ÙÚÈÎÒÓ Î·È Ó¢ÚÔÌÂÙ·‚ÔÏÈÎÒÓ
ΤÓÙÚˆÓ ÙÔ˘ ÂÛˆÙÂÚÈÎÔ‡ Î·È Â͈ÙÂÚÈÎÔ‡ ˘‹ÚÍ ÔχÙÈÌË.
∞ÔÙÂϤÛÌ·Ù·
™ÙÔÓ ¶›Ó·Î· 1 Ê·›ÓÂÙ·È Ô ·ÚÈıÌfi˜ ÙˆÓ ·ÛıÂÓÒÓ ·Ó¿ ηÙËÁÔÚ›· ÎÚÈÙËÚ›ˆÓ, Û‡Ìʈӷ Ì ٷ ÔÔ›· ÔÈ
ÁÈ·ÙÚÔ› Ù˘ ÚˆÙÔ‚¿ıÌÈ·˜ ÊÚÔÓÙ›‰·˜ ˘Á›·˜ ·Ú¤ÂÌ„·Ó ÙÔ˘˜ ·ÛıÂÓ›˜ ÛÙÔ ¶·ÓÂÈÛÙËÌÈ·Îfi ¡ÔÛÔÎÔÌ›Ô. ¶·Ú·¤ÌÊıËÎ·Ó Û˘ÓÔÏÈο 112 ·ÛıÂÓ›˜, 17 (15,2%) ·fi ÙÔ˘˜ ÔÔ›Ô˘˜ ‰È·ÈÛÙÒıËΠfiÙÈ Â›¯·Ó
ÁÓˆÛÙfi ÌÂÙ·‚ÔÏÈÎfi ÓfiÛËÌ·. ∏ ÓÔËÙÈ΋ ηı˘ÛÙ¤ÚËÛË (49 ·ÛıÂÓ›˜) Î·È ÔÈ Â›ÌÔÓÔÈ Û·ÛÌÔ› (36 ·ÛıÂÓ›˜) ‹Ù·Ó Ù· Û˘ÓËı¤ÛÙÂÚ· Û˘ÌÙÒÌ·Ù· ‹ ¯·Ú·-
ÁÈ· Ù· ÔÔ›· ÔÈ ·ÛıÂÓ›˜ ·Ú·¤ÌÊıËηÓ. ∆· Û˘ÓËı¤ÛÙÂÚ· ·fi Ù· ÌË Ó¢ÚÔÏÔÁÈο Û˘-
‹ ¯·Ú·ÎÙËÚÈÛÙÈο Ô˘ ¤ıÂÛ·Ó ÙËÓ ˘fi-
ÌÂÙ·‚ÔÏÈÎÔ‡ ÓÔÛ‹Ì·ÙÔ˜ ‹Ù·Ó Ë ·‰È¢ÎÚ›ÓÈÛÙ˘
¤ˆ˜ ÙfiÙÂ, ηı˘ÛÙ¤ÚËÛË Ù˘ ·Ó¿Ù˘Í˘ Î·È ÙÔ Â›ÌÔÓÔ ¤Î˙ÂÌ·. ∆· Û˘¯ÓfiÙÂÚ· ÌÂÙ·‚ÔÏÈο ÓÔÛ‹Ì·Ù· Ô˘ ‰È·ÁÓÒÛıËÎ·Ó ‹Ù·Ó ÔÈ ÔÚÁ·ÓÈΤ˜ ÔÍÂÔ˘Ú›Â˜. ¢È·ÁÓÒÛÙËÎ·Ó Û˘ÓÔÏÈο 8 ·ÛıÂÓ›˜ Ì ÔÚÁ·ÓÈ΋ ÔÍÂÔ˘Ú›· (47%), 3 ·ÛıÂÓ›˜ Ì ÁÏ˘ÎÔÁÔÓÈ¿ÛÂȘ (17,6%), 2 ·ÛıÂÓ›˜ ̠ϢÎÔ‰˘ÛÙÚÔÊ›· (11,7%), 2 ·ÛıÂÓ›˜ ÌÂ Ï˘ÛÔÛÛˆÌȷο ÓÔÛ‹Ì·Ù· (11,7%), 1 ·ÛıÂÓ‹˜ Ì ‰È·Ù·Ú·¯¤˜ ÛÙÔ ÌÂÙ·‚ÔÏÈÛÌfi
ÙˆÓ ·ÌÈÓÔͤˆÓ (5,8%) Î·È 1 ·ÛıÂÓ‹˜ Ì ÌÈÙÔ¯ÔÓ‰ÚÈÔ¿ıÂÈ· (5,8%). ∆· ÓÔÛ‹Ì·Ù· Ô˘ ‰È·ÁÓÒÛıËÎ·Ó Î·È Ë ËÏÈΛ· ÙˆÓ ·ÛıÂÓÒÓ Ê·›ÓÔÓÙ·È ÛÙÔÓ ¶›Ó·Î· 2.
™˘˙‹ÙËÛË
∏ ·ÚÔ‡Û· ÈÏÔÙÈ΋ ÌÂϤÙË ‰ÂÓ ÛÙÂÚÂ›Ù·È ÌÂıÔ‰ÔÏÔÁÈÎÒÓ ÂÚÈÔÚÈÛÌÒÓ. O ÌÈÎÚfi˜ ·ÚÈıÌfi˜ ÙˆÓ
(%)
OÚÁ·ÓÈ΋ Ô͢Ԣڛ· 8 (47%)
ªÂı˘ÏÌ·ÏÔÓÈ΋ Ô͢Ԣڛ· (6 ÌËÓÒÓ)
ªÂı˘ÏÌ·ÏÔÓÈ΋ Ô͢Ԣڛ· (10 ÌËÓÒÓ)
LCHAD (10 ÌËÓÒÓ)
MCAD (11 ÌËÓÒÓ)
∞Ó¿ÚÎÂÈ· ‚ÈÔÙÈÓȉ¿Û˘ (2,5 ÂÙÒÓ)
ÀÂÚÔÍ·ÏÔ˘Ú›· (3 ÂÙÒÓ)
2-ÔÍÔÁÏÔ˘Ù·ÚÈ΋ Ô͢Ԣڛ· (5 ÂÙÒÓ)
°ÏÔ˘Ù·ÚÈ΋ Ô͢Ԣڛ· Ù‡Ô˘ I (13 ÂÙÒÓ)
°Ï˘ÎÔÁÔÓÈ¿ÛÂȘ
°Ï˘ÎÔÁÔÓ›·ÛË Ù‡Ô˘ πa (15 ÂÙÒÓ)
°Ï˘ÎÔÁÔÓ›·ÛË Ù‡Ô˘ III (21 ÂÙÒÓ)
°Ï˘ÎÔÁÔÓ›·ÛË Ù‡Ô˘ Ib (26 ÂÙÒÓ)
3 (17,6%)
§Â˘ÎÔ‰˘ÛÙÚÔʛ˜ 2 (11,7%)
¡fiÛÔ˜ Canavan (12 ÌËÓÒÓ)
º˘ÏÔÛ‡Ó‰ÂÙË ·‰ÚÂÓÔÏ¢ÎÔ‰˘ÛÙÚÔÊ›· (8 ÂÙÒÓ)
§˘ÛÔÛÛˆÌȷο ÓÔÛ‹Ì·Ù·2 (11,7%)
∞Ó¿ÚÎÂÈ· ·-Ì·ÓÓÔÛȉ¿Û˘ (3 ÂÙÒÓ)
¡fiÛÔ˜ Gaucher Ù‡Ô˘ I (30 ÂÙÒÓ)
¢È·Ù·Ú·¯¤˜ ÛÙÔ ÌÂÙ·‚ÔÏÈÛÌfi ÙˆÓ ·ÌÈÓÔͤˆÓ1 (5,8%)
¡fiÛÔ˜ ÔÛÌ‹˜ Ô‡ÚˆÓ ÛÊÂÓ‰¿ÌÔ˘ (Maple syrup disease) (2 ÌËÓÒÓ)
ªÈÙÔ¯ÔӉȷΤ˜ ÂÁÎÂÊ·ÏÔ¿ıÂȘ1 (5,8%)
™˘Ó‰˘·Ṳ̂ÓË ·Ó¿ÚÎÂÈ· ÙÔ˘ Û˘ÌϤÁÌ·ÙÔ˜ π Î·È πππ (2 ÂÙÒÓ)
™‡ÓÔÏÔ ·ÛıÂÓÒÓ Ô˘ ‰È·ÁÓÒÛıËηÓ17
˘¤ÊÂÚ ·fi ÙËÓ ÎÏ·ÛÈ΋ ÌÔÚÊ‹ Ù˘ ÓfiÛÔ˘ Gaucher. ∏ ÓfiÛÔ˜ Gaucher Â›Ó·È ÙÔ Û˘¯ÓfiÙÂÚÔ ·fi Ù· Ï˘ÛÔÛÛˆÌȷο ÓÔÛ‹Ì·Ù· Î·È ·ÚÔ˘ÛÈ¿˙ÂÈ ÌÂÁ¿ÏË ÎÏÈÓÈ΋ ÂÙÂÚÔÁ¤ÓÂÈ· (17). H ·ÛıÂÓ‹˜ Ì ÓfiÛÔ Gaucher ÛÙË ÌÂϤÙË ·˘Ù‹ ‰È·ÁÓÒÛıËΠ۠ÌÂÁ¿ÏË
Û¯ÂÙÈο ËÏÈΛ· Î·È ·Ú·¤ÌÊıËΠÛÙË ÌÔÓ¿‰· ÌÂÙ·‚ÔÏÈÎÒÓ ÓÔÛËÌ¿ÙˆÓ ÏfiÁˆ Ù˘ ÛÔ‚·Ú‹˜ ηı˘ÛÙ¤ÚËÛ˘ Ù˘ ·Ó¿Ù˘Í˘, ·fiÙÔÎÔ Ù˘ ¯ÚfiÓÈ·˜ ÓfiÛÔ˘.
¶¤Ú·Ó ÙˆÓ Ù˘ÈÎÒÓ ·ÈÌ·ÙÔÏÔÁÈÎÒÓ Î·È ÔÛÙÈÎÒÓ ·ÏÏÔÈÒÛÂˆÓ Ù˘ ÓfiÛÔ˘, ·ÚÔ˘Û›·˙ ÂÈϤÔÓ Â›ÌÔÓË ÂÎ˙ÂÌ·ÙÔÂȉ‹ ‰ÂÚÌ·Ù›Ùȉ· ¿ÎÚˆÓ Î·È ÚÔÛÒÔ˘.
¶·Ú’ fiÏÔ Ô˘ Û ·ÛıÂÓ›˜ Ì ¿ÏÏ· Ï˘ÛÔÛÛˆÌȷο ÓÔÛ‹Ì·Ù· (fiˆ˜ ÔÈ Á·ÁÁÏÈÔÛȉÒÛÂȘ GM1) Ë ¤Îı˘ÛË ÂÍ·ÓıËÌ¿ÙˆÓ ÂÚÈÁÚ¿ÊÂÙ·È ÛÙËÓ Ù˘È΋ ÎÏÈÓÈ΋ ÂÈÎfiÓ· Ù˘ ÓfiÛÔ˘, ÛÙË ÓfiÛÔ Gaucher Ë Û˘ÌÌÂÙÔ¯‹ ÙÔ˘ ‰¤ÚÌ·ÙÔ˜ ı· Ú¤ÂÈ Ó· ıˆÚËı› ¿Ù˘Ë Ê·ÈÓÔÙ˘È΋ ÂΉ‹ÏˆÛË Î·È Ì¤¯ÚȘ ·Ô‰Â›Íˆ˜ ÙÔ˘ ÂÓ·ÓÙ›Ô˘ ‰ÂÓ ı· Ú¤ÂÈ Ó· Û˘Û¯ÂÙ›˙ÂÙ·È Ì ÙË ÓfiÛÔ. ∏ Û˘ÛÛÒÚ¢ÛË ÙÔ˘ ÁÏ˘ÎÔÛÂÚ‚ÚÔÛȉ›Ô˘ ÛÙÔÓ Ì˘ÂÏfi Ô‰‹ÁËÛ Û ·Ó·ÈÌ›·, Ï¢ÎÔÂÓ›· Î·È ıÚÔÌ‚Ô΢ÙÙ·ÚÔÂÓ›·. §fiÁˆ Ù˘ Û˘ÌÌÂÙÔ¯‹˜ ÙÔ˘ Ì˘ÂÏÔ‡ Ì ·ÎfiÏÔ˘ıË ·Ó΢ÙÙ·ÚÔÂÓ›· ¯ˆÚ›˜ ÚÔÛ‚ÔÏ‹ ÙÔ˘ ÎÂÓÙÚÈÎÔ‡ Ó¢ÚÈÎÔ‡ Û˘ÛÙ‹Ì·ÙÔ˜, Ë ·ÛıÂÓ‹˜ Ù¤ıËΠ۠ÂÓ˙˘ÌÈ΋ ıÂڷ›· ˘ÔηٿÛÙ·Û˘ (18,19).
ŒÓ·˜ ·ÛıÂÓ‹˜ Ì ÓfiÛÔ ÔÛÌ‹˜ Ô‡ÚˆÓ ÛÊÂÓ‰¿ÌÔ˘ (Maple syrup disease) ‰È·ÁÓÒÛıËΠ¤ÁηÈÚ· Û ÌÈÎÚ‹ ËÏÈΛ· Î·È Ì ÙËÓ Î·Ù¿ÏÏËÏË ıÂڷ¢ÙÈ΋
‰È·ÁÓÒÛıËΠÌÈÙÔ¯ÔÓ‰ÚÈÔ¿ıÂÈ· ‰ÂÓ Î·Ù¤ÛÙË ‰˘Ó·Ù‹ Ë ÂÊ·ÚÌÔÁ‹ Û˘Ì‚Ô˘Ï¢ÙÈ΋˜ ÁÂÓÂÙÈ΋˜, ÏfiÁˆ ÙÔ˘ ÔχÏÔÎÔ˘ ÙÚfiÔ˘ Ì ÙÔÓ ÔÔ›Ô ÎÏËÚÔÓÔÌÔ‡ÓÙ·È ÔÈ ÌÈÙÔ¯ÔÓ‰ÚÈÔ¿ıÂȘ (20,21). ∏ ·ÓÙÈÌÂÙÒÈÛË ‹Ù·Ó Û˘Ìو̷ÙÈ΋, ÂÓÒ
ÛÙËÓ ÔÈÎÔÁ¤ÓÂÈ· ·Ú·Û¯¤ıËΠοı „˘¯ÔÏÔÁÈ΋ Î·È ÔÈÎÔÓÔÌÈ΋ ˘ÔÛÙ‹ÚÈÍË. ™˘Ìو̷ÙÈ΋ ıÂڷ›·, „˘¯ÔÏÔÁÈ΋ Î·È ÎÔÈÓˆÓÈÎÔÔÈÎÔÓÔÌÈ΋ ˘ÔÛÙ‹ÚÈÍË ·Ú·Û¯¤ıËΠ۠fiÏÔ˘˜ ÙÔ˘˜ ·ÛıÂÓ›˜ Ù˘ ÌÂϤÙ˘, ·ÓÂÍ¿ÚÙËÙ· ·fi ÙÔ ·Ó Ù¤ıËΠ‹ fi¯È Ë ‰È¿ÁÓˆÛË ÁÓˆÛÙÔ‡ ÌÂÙ·‚ÔÏÈÎÔ‡ ÓÔÛ‹Ì·ÙÔ˜. ™Â fiÏË ·˘Ù‹ ÙËÓ ÚÔÛ¿ıÂÈ·, Ë Û˘Ì‚ÔÏ‹ ÙˆÓ È·ÙÚÒÓ Ù˘ ÁÂÓÈ΋˜ È·ÙÚÈ΋˜ Î·È ÙˆÓ ·È‰È¿ÙÚˆÓ Ô˘ ÂÚÁ¿˙ÔÓÙ·È ÛÙ· ΤÓÙÚ· ÚˆÙÔ‚¿ıÌÈ·˜ ÊÚÔÓÙ›‰·˜
˘Á›·˜ ‹Ù·Ó Ôχ ÌÂÁ¿ÏË. ÷ڷÎÙËÚÈÛÙÈο ·Ó·Ê¤-
ÚÂÙ·È fiÙÈ Ù· ÚÒÙ· 2 ¯ÚfiÓÈ· ÏÂÈÙÔ˘ÚÁ›·˜ Ù˘ ÌÔÓ¿‰·˜ ÌÂÙ·‚ÔÏÈÎÒÓ ÓÔÛËÌ¿ÙˆÓ ·Ú·¤ÌÊıËÎ·Ó ÛÙÔ
¶·ÓÂÈÛÙËÌÈ·Îfi ¡ÔÛÔÎÔÌÂ›Ô ÙÔ˘ ∏Ú·ÎÏ›Ԣ ÌfiÓÔ 70 ·ÛıÂÓ›˜, ·fi ÙÔ˘˜ ÔÔ›Ô˘˜ ÌfiÓÔ 21 (30%) ‹Ù·Ó ·fi ÙËÓ ‡·ÈıÚÔ. ™ÙȘ ·ÁÚÔÙÈΤ˜ ÂÚÈÔ¯¤˜ Ù˘
∫Ú‹Ù˘, ÌÂÚÈΤ˜ ·fi ÙȘ Ôԛ˜ Â›Ó·È ¿ÎÚˆ˜ ·ÔÌÔӈ̤Ó˜, ÂÈÎÚ·ÙÔ‡Ó È‰È¿˙Ô˘Û˜ ÎÔÈÓˆÓÈΤ˜ Î·È ÔÏÈÙÈÛÌÈΤ˜ Û˘Óı‹Î˜ Î·È Ë Â·Ê‹ Ì ÙÔÓ È·ÙÚfi Â›Ó·È Û˘¯Ó¿ ÂÍ·ÈÚÂÙÈο ‰‡ÛÎÔÏË. ™Â ÔÏϤ˜ ÔÈÎÔÁ¤-
‰˘ÛÎÔϛ˜ ÛÙËÓ ÎÔÈÓˆÓÈÎÔÔÈÎÔÓÔÌÈ΋ ·ÔηٿÛÙ·-
ÛË fiÏˆÓ ÙˆÓ ÌÂÏÒÓ Ù˘ ÔÈÎÔÁ¤ÓÂÈ·˜ (Á¿ÌÔ˜, ‡ÚÂ-
ÛË ÂÚÁ·Û›·˜). ∏ ·ÙÂÏ‹˜ Î·È ÂÛÊ·Ï̤ÓË Û˘¯Ó¿ ·ÓÙ›-
ÏË„Ë Î·È ÂÓË̤ڈÛË ÙÔ˘ ÏËı˘ÛÌÔ‡ Ù˘ ÂÚÈʤ-
ÚÂÈ·˜ ÁÈ· Ù· ÓÔÛ‹Ì·Ù· ·˘Ù¿, ÛÂ Û˘Ó‰˘·ÛÌfi Ì ÙËÓ
·ÙÂÏ‹ Âη›‰Â˘ÛË ÙˆÓ ÁÈ·ÙÚÒÓ, ηıÈÛÙÔ‡Ó ÙȘ ‰È·-
ÛÙ¿ÛÂȘ ÙÔ˘ ÚÔ‚Ï‹Ì·ÙÔ˜ ·ÎfiÌ· ÌÂÁ·Ï‡ÙÂÚ˜.
ªÂ ÙË Û˘ÌÌÂÙÔ¯‹ ÛÙË ÌÂϤÙË ·˘Ù‹, ÔÈ ÁÈ·ÙÚÔ›
Ù˘ ÚˆÙÔ‚¿ıÌÈ·˜ ÊÚÔÓÙ›‰·˜ ˘Á›·˜ ÂÓËÌÂÚÒıË-
Î·Ó Î·È Âηȉ‡ÙËÎ·Ó Û¯ÂÙÈο Ì ÙË ‰È¿ÁÓˆÛË Î·È
ÙȘ ‰˘Ó·ÙfiÙËÙ˜ ·ÓÙÈÌÂÙÒÈÛ˘ Î·È ÁÂÓÂÙÈ΋˜ Û˘Ì-
‚Ô˘Ï¢ÙÈ΋˜ ÛÙ· ÌÂÙ·‚ÔÏÈο ÓÔÛ‹Ì·Ù·. ∞˘ÙÔ› Ì ÙË
ÛÂÈÚ¿ ÙÔ˘˜, ÏfiÁˆ Ù˘ ηχÙÂÚ˘ ·ʋ˜ Ô˘
¤¯Ô˘Ó Ì ÙÔ˘˜ ηÙÔ›ÎÔ˘˜ ÙˆÓ ·ÁÚÔÙÈÎÒÓ ÂÚÈÔ¯ÒÓ, ÌfiÚÂÛ·Ó Ó· ¢·ÈÛıËÙÔÔÈ‹ÛÔ˘Ó ÙÔÓ ÏËı˘ÛÌfi
Ù˘ ˘·›ıÚÔ˘ ÁÈ· ÙËÓ ÂÈÙ·ÎÙÈ΋ ·Ó¿ÁÎË ÂϤÁ¯Ô˘,
fiÔ˘ Ù¤ıËΠ˘fiÓÔÈ· Ù¤ÙÔÈÔ˘ ÓÔÛ‹Ì·ÙÔ˜. OÈ ÁÈ·-
ÙÚÔ› Ù˘ ÚˆÙÔ‚¿ıÌÈ·˜ ÊÚÔÓÙ›‰·˜ ˘Á›·˜ ·Ú¤Â-
Ì·Ó ÙÔ˘˜ ·ÛıÂÓ›˜ Ì ˘fiÓÔÈ· ÌÂÙ·‚ÔÏÈÎÔ‡ ÓÔÛ‹-
Ì·ÙÔ˜ ÛÙÔ ¶·ÓÂÈÛÙËÌÈ·Îfi ¡ÔÛÔÎÔÌÂ›Ô ∏Ú·ÎÏ›Ԣ. ªÂ ÙË Û˘ÓÂÚÁ·Û›· ÙˆÓ ÓÔÛÔÎÔÌÂÈ·ÎÒÓ È·ÙÚÒÓ
Î·È ÙˆÓ È·ÙÚÒÓ Ù˘ ÚˆÙÔ‚¿ıÌÈ·˜ ÊÚÔÓÙ›‰·˜ ˘Á›-
ÙÂÎÌËÚÈÒıËΠ‰È¿ÁÓˆÛË ÌÂÙ·‚ÔÏÈÎÔ‡ ÓÔÛ‹Ì·ÙÔ˜ Û 17 ·fi 112 ·ÛıÂÓ›˜ Ô˘ ·Ú·¤ÌÊıËηÓ.
ŸÏÔÈ ÔÈ ·ÛıÂÓ›˜ ·Ú·ÎÔÏÔ˘ıÔ‡ÓÙ·È ÛÙË ªÔÓ¿‰·
¡ÔÛËÌ¿ÙˆÓ
Û¯Âı› οı ‰˘Ó·Ù‹ ‚Ô‹ıÂÈ·. ™ÙÔÓ ÂÓÙÔÈÛÌfi ÙˆÓ
“‡ÔÙˆÓ”·ÙfiÌˆÓ ‚Ô‹ıËÛ ȉȷ›ÙÂÚ· ÙÔ ÂÚˆÙËÌ·-
ÙÔÏfiÁÈÔ Ô˘ ¯ÚËÛÈÌÔÔÈ‹ıËÎÂ. ∆Ô ÂÚˆÙËÌ·ÙÔÏfiÁÈÔ
·˘Ùfi, ·Ó Î·È ‰ÂÓ Â›Ó·È Ï‹Ú˜, ÌÔÚ› Ó· ıˆÚËı›
ηٿÏÏËÏÔ ÁÈ· ÙÔ˘˜ ÁÈ·ÙÚÔ‡˜ Ù˘ ÚˆÙÔ‚¿ıÌÈ·˜
ÊÚÔÓÙ›‰·˜ ˘Á›·˜ ÏfiÁˆ ÙÔ˘ fiÙÈ Â›Ó·È Û‡ÓÙÔÌÔ, ·Ïfi
Î·È ·ÚÔ˘ÛÈ¿˙ÂÈ ˘„ËÏ‹ ¢·ÈÛıËÛ›·, fiˆ˜ ·Ô‰Â›-
¯ıËΠ·fi ÙÔ Û¯ÂÙÈο ˘„ËÏfi ÔÛÔÛÙfi ‰È·ÁÓÒÛˆÓ
ÛÙÔ Û‡ÓÔÏÔ ÙˆÓ ·ÛıÂÓÒÓ Ô˘ ·Ú·¤ÌÊıËηÓ.
™˘ÌÂÚ·ÛÌ·ÙÈο, Ë Û˘Ì‚ÔÏ‹ Ù˘ Û˘ÓÂÚÁ·Û›·˜
ÙˆÓ ÁÈ·ÙÚÒÓ Ù˘ ÚˆÙÔ‚¿ıÌÈ·˜ ÊÚÔÓÙ›‰·˜ ˘Á›·˜
Î·È ÙˆÓ ÓÔÛÔÎÔÌÂÈ·ÎÒÓ ÁÈ·ÙÚÒÓ Ê·›ÓÂÙ·È ÛËÌ·ÓÙÈ-
΋ ÛÙËÓ ¤ÁηÈÚË ‰È¿ÁÓˆÛË, ıÂڷ¢ÙÈ΋ ·ÓÙÈÌÂÙÒ-
ÈÛË, ÁÂÓÂÙÈ΋ Û˘Ì‚Ô˘Ï¢ÙÈ΋ Î·È ÎÔÈÓˆÓÈÎÔÔÈÎÔÓÔÌÈ΋ ˘ÔÛÙ‹ÚÈÍË ·ÛıÂÓÒÓ Î·È ÔÈÎÔÁÂÓÂÈÒÓ Ì ÌÂÙ·-
‚ÔÏÈο ÓÔÛ‹Ì·Ù·. ∏ ÚÔÛÂÎÙÈ΋ ·ÍÈÔÏfiÁËÛË ÂÓfi˜
·ÚÈıÌÔ‡ ÎÏÈÓÈÎÒÓ ¯·Ú·ÎÙËÚÈÛÙÈÎÒÓ ‹ Û˘Ìو̿وÓ
ÌÔÚ› Ó· Ô‰ËÁ‹ÛÂÈ ÛÙËÓ ¤ÁηÈÚË ‰È¿ÁÓˆÛË Î·È ¤Ì-
ÌÂÛ· ÛÙËÓ ¤ÁηÈÚË ıÂڷ¢ÙÈ΋ ·Ú¤Ì‚·ÛË, fiÔ˘ ·˘Ù‹ Â›Ó·È Û‹ÌÂÚ· ÂÊÈÎÙ‹. ŸÌˆ˜, ·ÎfiÌË Î·È fiÙ·Ó ÔÈ
‰˘Ó·ÙfiÙËÙ˜ ıÂڷ¢ÙÈ΋˜ ·Ú¤Ì‚·Û˘ Â›Ó·È Â-
Pediatrics 2000;105:e10.
2. Zakiah I, Ashikin YN, Aisiah SM, Ismail HI. Inborn errors of metabolic diseases in Malaysia: a preliminary report of maple syrup urine diseases for 1993. Southeast Asian J Trop Med Pubic Health 1995;26 (Suppl 1):134-136.
3. Kaur M, Das GP, Verma IC. Inborn errors of amino acid metabolism in north India. J Inherit Metab Dis 1994;17:230233.
4. Widhalm K. 25 years Austrian screening program for inborn errors of metabolism at the Vienna University. Wien Klin Wochenschr 1992;104:510-513.
5. Toone JR, Applegarth DA, Vallance HD, Wilson RD. Early amniocentesis for biochemical genetic prenatal diagnosis. Lancet 1998;351:1207-1208.
6. Mathieu M. Prenatal diagnosis of genetic diseases in France. Ann Pharm Fr 1999;57:380-384.
7. ∂˘·ÁÁÂÏ›Ô˘ ∞, °È·ÓÓ·ÎÔÔ‡ÏÔ˘ Ã, ™Ì˘Ú¿ÎȘ ™. ¢È·ÁÓˆÛÙÈ΋ ÚÔۤϷÛË ÙˆÓ Ó¢ÚÔÂÎÊ˘ÏÈÛÙÈÎÒÓ Î·È ÌÂÙ·‚ÔÏÈÎÒÓ ÓÔÛËÌ¿ÙˆÓ ÙˆÓ ·È‰ÈÒÓ. ¶·È‰È·ÙÚÈ΋ 1995;58:456-461.
8. Snyderman SE. Clinical aspects of disorders of the urea cycle. Pediatrics 1981;68:284-289.
9. Rezvani I, Rosenblatt D. Metabolic diseases. An approach to inborn errors. In: Saunders Company, eds. Nelson Textbook of Pediatrics. 16th ed. Philadelphia, Pensylvania; 2000. p. 343-344.
10. ¢ÚÔÁοÚË ∂, ª·ÓˆÏ¿ÎË ¡, ¡·ÎÔÔ‡ÏÔ˘ §. °Ï˘ÎÔÁÔÓ›·ÛË Ù‡Ô˘ π· (ÂÌÂÈÚ›· 19 ÂÚÈÙÒÛÂˆÓ Û ·È‰È¿). π·ÙÚÈ΋ 1992;621:481-485.
11. ∂ÌÔÚÈ¿‰Ô˘ ª, ∞˘ÁÔ˘ÛÙ›‰Ô˘-™·‚‚ÔÔ‡ÏÔ˘ ¶, ∞ÔÛÙÔÏ›‰Ô˘ ∫, ∫·Úη‚¤Ï·˜ °, ¢ÚÔ˘ÛÈÒÙÔ˘ ∞, µ·ÚÏ¿Ì˘ °. ¶ÂÚÈÁÚ·Ê‹ ÂÚ›ÙˆÛ˘ ‚ÚÂÊÈÎÔ‡ Ù‡Ô˘ ÁÏ˘ÎÔÁÔÓ›·Û˘ Ù‡Ô˘ ππ. ¡fiÛÔ˜ Pompe. ¶·È‰È·ÙÚÈ΋ 1998;61:408-413.
12. ª¿ÓÙ˙ÈÔ˘ £, §È·ÎÔÔ‡ÏÔ˘ £, ¢ÚÔÁοÚË ∂, ∞ı·Ó·Û¿ÎË ∫, ∫·Ú·ÌԇϷ ∞, ∫·ÙÙ¿Ì˘ Ã. ∞ÒÙÂÚ˜ ÂÈÏÔΤ˜ ÁÏ˘ÎÔÁÔÓ›·Û˘ Ù‡Ô˘ π·. ¢ÂÏÙ ∞’ ¶·È‰È·ÙÚ ¶·Ó ∞ıËÓÒÓ 1998;45:166-171.
13. Rashed M, Ozand PT, al Aqeel A, Gascon GG. Experience of King Faisal Specialist Hospital and Research Center with Saudi organic acid disorders. Brain Dev 1994;16 (Suppl):16.
14. Lehnert W. Long-term results of selective screening for inborn errors of metabolism. Eur J Pediatr 1994;153 (Suppl 1):S9-13.
15. Norrgard KJ, Pomponio RJ, Hymes J, Wolf B. Mutations causing profound biotinidase deficiency in children ascertained by newborn screening in the United States occur at different frequencies than in symptomatic children. Pediatr Res 1999;46:20-27.
16. Colamaria V, Burlina AB, Gaburro D, Pajno-Ferrara F, Saudubray JM, Merino RG et al. Biotin-responsive infantile encephalpathy: EEG-polygraphic study of a case. Epilepsia 1989;30:573-578.
17. Moraitou M, van Weely S, Verhoek M, Aerts J, Dimitriou E, Michelakakis H. The facile detection of 1505G A in Gaucher patients with different phenotypes. Biochim Biophys Acta 2001;1536:97-102.
1. Applegarth DA, Toone JR, Lowry RB. Incidence of inborn errors of metabolism in British Columbia, 1969-1996.
18. Ida H, Rennert OM, Kato S, Ueda T, Oishi K, Maekawa K et al. Severe skeletal complications in Japanese patients with
type I Gaucher disease. J Inherit Metab Dis 1999;22:63-73.
19. Maaswinkel-Mooij P, Hollak C, van Eysden-Plaisier M, Prins M, Aerts H, Poll R. The natural course of Gaucher disease in The Netherlands: implications for monitoring of disease manifestations. J Inherit Metab Dis 2000;23:77-82.
20. Howell N. Human mitochondrial diseases: answering questions and questioning answers. Int Rev Cytol 1999;186:49-116.
21. Santorelli FM, Tanji K, Shanske S, Krishna S, Schmidt RE, Greenwood RS et al. The mitochondrial DNA A8344G mutation in Leigh syndrome revealed by analysis in paraffin-
embedded sections: revisiting the past. Ann Neurol 1998;44:962-964.
HÌÂÚÔÌËÓ›· ˘Ô‚ÔÏ‹˜: 22-03-2002
HÌÂÚÔÌËÓ›· ¤ÁÎÚÈÛ˘: 20-12-2002
¢È‡ı˘ÓÛË ·ÏÏËÏÔÁÚ·Ê›·˜: ªÈ¯·ËÏ›‰Ô˘ ∂ϤÓË
¶·È‰È·ÙÚÈ΋ ∫ÏÈÓÈ΋
¶ÂÚÈÊÂÚÂÈ·Îfi ¶·ÓÂÈÛÙËÌÈ·Îfi °ÂÓÈÎfi ¡ÔÛÔÎÔÌ›Ô
∏Ú¿ÎÏÂÈÔ, ∫Ú‹ÙË
™ÎÔfi˜: ™ÎÔfi˜ Ù˘ ·ÚÔ‡Û·˜ ÌÂϤÙ˘ Ù˘ ·Ó¿Ù˘Í˘ Î·È Ù˘ ‰È·ÙÚÔÊÈ΋˜ ηٿÛÙ·Û˘ ·È‰ÈÒÓ Ì ÙÚÔÊÈΤ˜ ·ÏÏÂÚÁ›Â˜
ÙÚÔÊÈΤ˜ ·ÏÏÂÚÁ›Â˜ ÂËÚ¿˙Ô˘Ó ÙËÓ ·Ó¿Ù˘ÍË ÙˆÓ ·È‰ÈÒÓ.
ÀÏÈÎfi Î·È Ì¤ıÔ‰ÔÈ: °È· ÙÔÓ Î·ıÔÚÈÛÌfi Èı·ÓÒÓ ÚÔ‚ÏËÌ¿ÙˆÓ
·Ó¿Ù˘Í˘ ¯ÚËÛÈÌÔÔÈ‹ıËÎ·Ó ÌÂÙÚ‹ÛÂȘ ‡„Ô˘˜, ‚¿ÚÔ˘˜ ηÈ
‰Â›ÎÙË Ì¿˙·˜ ÛÒÌ·ÙÔ˜. OÈ ÂÎÙÈÌ‹ÛÂȘ ÁÈ· ÙËÓ ÂÓ¤ÚÁÂÈ· Î·È Ù·
ıÚÂÙÈο Û˘ÛÙ·ÙÈο ‚·Û›ÛÙËÎ·Ó Û ÙÚÈ‹ÌÂÚ· ËÌÂÚÔÏfiÁÈ· η-
Ù·ÁÚ·Ê‹˜ ÙÚÔʛ̈Ó. ŒÓ· ÂÚˆÙËÌ·ÙÔÏfiÁÈÔ ¯ÚËÛÈÌÔÔÈ‹ıËÎÂ
ÁÈ· ÙÔÓ Î·ıÔÚÈÛÌfi ÙÔ˘ ·ÚÈıÌÔ‡ ÙˆÓ ÙÚÔÊÈÎÒÓ ·ÏÏÂÚÁÈÒÓ Î·È
¿ÏÏˆÓ ÌÂÙ·‚ÏËÙÒÓ. ™Â ·˘Ù‹ ÙËÓ ÚÔÔÙÈ΋, ‰È·ÛÙ·˘ÚÔ‡ÌÂÓË
ÌÂϤÙË Û˘ÌÌÂÙ›¯·Ó 99 ·È‰È¿ Ì ÙÚÔÊÈΤ˜ ·ÏÏÂÚÁ›Â˜ (·ÛıÂÓ›˜) Ì ̤ÛË ËÏÈΛ· Ù· 3,7±2,3 ¤ÙË Î·È 99 ·È‰È¿ ¯ˆÚ›˜ ÙÚÔÊÈΤ˜ ·ÏÏÂÚÁ›Â˜ (‰Â›ÁÌ· ·Ó·ÊÔÚ¿˜) Ì ̤ÛË ËÏÈΛ· Ù· 4,1±2,4 ¤ÙË. ∏ ÛÙ·ÙÈÛÙÈ΋ ·Ó¿Ï˘ÛË ‰ÈÂÍ‹¯ıË Ì ÙÔ CochranMantel-Haeszel Statistics, ¯ÚËÛÈÌÔÔÈÒÓÙ·˜ ÁÂÓÈ΋ Û˘Û¯¤ÙÈÛË Î·È Fisher Exact Test.
∞ÔÙÂϤÛÌ·Ù·: ∆· ·È‰È¿ Ì ‰‡Ô ‹ ÂÚÈÛÛfiÙÂÚ˜ ÙÚÔÊÈΤ˜ ·ÏÏÂÚÁ›Â˜ ›¯·Ó ¯·ÌËÏfiÙÂÚÔ ·Ó¿ÛÙËÌ·, Ì ÎÚÈÙ‹ÚÈÔ ÙȘ η̇Ϙ ‡„Ô˘˜-ËÏÈΛ·˜, Û ۯ¤ÛË Ì ÂΛӷ Ì ̛· ÙÚÔÊÈ΋ ·ÏÏÂÚÁ›· (p<0,05). ¶ÂÚÈÛÛfiÙÂÚÔ ·fi ÙÔ 2,5% ÙˆÓ ·È‰ÈÒÓ Î·È ÙˆÓ ‰‡Ô ÔÌ¿‰ˆÓ ηٷӿψÓ ÏÈÁfiÙÂÚÔ ·fi 6,7% Ù˘ ËÌÂÚ‹ÛÈ·˜ Û˘ÓÈÛÙÒÌÂÓ˘ ÔÛfiÙËÙ·˜ ÁÈ· ÙÔ ·Û‚¤ÛÙÈÔ, ÙË ‚ÈÙ·Ì›ÓË D Î·È ÙË ‚ÈÙ·Ì›ÓË ∂. ¶ÂÚÈÛÛfiÙÂÚ· ·È‰È¿ Ì ·ÏÏÂÚÁ›· ÛÙÔ Á¿Ï· ·ÁÂÏ¿‰·˜ ‹ ÔÏϷϤ˜ ·ÏÏÂÚÁ›Â˜ Î·Ù·Ó¿ÏˆÓ·Ó ÏÈÁfiÙÂÚÔ ·Û‚¤ÛÙÈÔ
ÚfiÛÏ˄˘ ·Û‚ÂÛÙ›Ô˘ Î·È ‚È-
Ì ÙÚÔÊÈ΋ ·ÏÏÂÚÁ›· ‹Ù·Ó ÏÈÁfiÙÂÚË, ·Ó ÙÔ ·È‰› ÂÏ¿Ì‚·Ó ‰È·ÙÚÔÊÈΤ˜ Û˘Ì‚Ô˘Ï¤˜ (p<0,05) ‹ ηٷӿψÓ ¤Ó· ·ÛʷϤ˜ ‚ÚÂÊÈÎfi/ÓÂÔÁÓÈÎfi ˘ÔηٿÛÙ·ÙÔ ‹ ˘ÔηٿÛÙ·ÙÔ ÛfiÁÈ·˜.
™˘ÌÂÚ¿ÛÌ·Ù·: ¶·È‰È¿ Ì ‰È·ÁÓˆṲ̂Ó˜ ÙÚÔÊÈΤ˜ ·ÏÏÂÚÁ›Â˜
¯ÚÂÈ¿˙ÔÓÙ·È ÂÙ‹ÛÈ· ‰È·ÙÚÔÊÈ΋ ·ÍÈÔÏfiÁËÛË ÁÈ· ÙËÓ ÚfiÏË„Ë ÚÔ‚ÏËÌ¿ÙˆÓ ·Ó¿Ù˘Í˘ ‹ ·Ó·ÚÎÔ‡˜ ÚfiÛÏ˄˘ ıÚÂÙÈ-
ÎÒÓ Û˘ÛÙ·ÙÈÎÒÓ. ∆· ·È‰È¿ Ì ·ÏÏÂÚÁ›· ÛÙÔ Á¿Ï· ‹ ÔÏϷϤ˜ ·ÏÏÂÚÁÈΤ˜ ·ÓÙȉڿÛÂȘ Â›Ó·È Û ÌÂÁ·Ï‡ÙÂÚÔ Î›Ó‰˘ÓÔ. ∏
‰È·ÙÚÔÊÈ΋ Âη›‰Â˘ÛË Â›Ó·È ··Ú·›ÙËÙË ÁÈ· ÙËÓ ·ÔÊ˘Á‹
fiÏˆÓ ÙˆÓ ÌÔÚÊÒÓ ÙÔ˘ ·ÏÏÂÚÁÈÔÁfiÓÔ˘ Î·È ÙËÓ ÂÓۈ̿وÛË ÂÓ·ÏÏ·ÎÙÈÎÒÓ ıÚÂÙÈÎÒÓ ÙÚÔÊÒÓ. O ÏËı˘ÛÌfi˜ ·˘Ùfi˜ ı·
ÌÔÚÔ‡Û ӷ ˆÊÂÏËı› ·fi ÙËÓ ·Ó¿Ù˘ÍË Î·È ÂÎÙ›ÌËÛË ÂÓfi˜
ÎÏÈÓÈÎÔ‡ ‰È·ÙÚÔÊÈÎÔ‡ ıÂڷ¢ÙÈÎÔ‡ ÚˆÙÔÎfiÏÏÔ˘.
1Christie L, Hine RJ, Parker JG, Burks W Food allergies in children affect nutrient intake and growth J Am Diet Assoc 2002;102:1648-1651
∞ÈÌÈÏ›· µ·ÛÈÏÔÔ‡ÏÔ˘
∞¡∞™∫O¶∏™∏REVIEW ARTICLE
Ó¤ˆÓ ÂÚ¢ÓËÙÈÎÒÓ ‰Â‰Ô̤ӈÓ
ª.™. §·Ú›Ô˘, §. ™Ù·ÌÔÁÈ¿ÓÓÔ˘
Idiopathic growth hormone deficiency in the light of new research data
M.S. Lariou, L. Stamoyannou
¶ÂÚ›ÏË„Ë: À¿Ú¯Ô˘Ó ÌÂÚÈο ÌË ÔÚÁ·ÓÈο ·›ÙÈ·
Ù˘ ·Ó¿ÚÎÂÈ·˜ Ù˘ ·˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘ Ô˘ ÌÔÚÔ‡Ó Ó· ·Ô‰ÔıÔ‡Ó Û ÁÂÓÂÙÈΤ˜ ‰È·Ù·Ú·¯¤˜ ÙÔ˘
¿ÍÔÓ· ˘Ôı·Ï¿ÌÔ˘-˘fiÊ˘Û˘. ¶ÚfiÛÊ·Ù˜ ÌÂϤÙ˜ ¤ÙÚ„·Ó ÙËÓ Ù·˘ÙÔÔ›ËÛË ÂÓfi˜ ·ÚÈıÌÔ‡ ÁÔÓȉ›ˆÓ Ô˘ ÂÓ¤¯ÔÓÙ·È ¿ÌÂÛ· ÛÙËÓ ·Ó¿Ù˘ÍË Ù˘ ˘fiÊ˘Û˘ Î·È ÙȘ ÂÍ·ÚÙÒÌÂÓ˜ ·fi ·˘Ù‹ ÏÂÈÙÔ˘ÚÁ›Â˜. ŒÙÛÈ, ÛËÌÂȷΤ˜ ÌÂÙ·ÏÏ¿ÍÂȘ ÛÙ· ÁÔÓ›‰È· Ù˘ ·˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘ (growth hormone, GH) Î·È ÙÔ˘ ˘Ô‰Ô¯¤· ÙÔ˘ ·Ú¿ÁÔÓÙ· ¤ÎÏ˘Û˘ Ù˘ ·˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘ (GH-releasing hormone receptor gene, GHRH) ¤¯Ô˘Ó ÂÚÈÁÚ·Ê› Û·Ó ·›ÙÈ· Ù˘ ÌÂÌÔӈ̤Ó˘ ·Ó¿ÚÎÂÈ·˜ ·˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘. ∞˘Ù¤˜ ÔÈ ‰È·Ù·Ú·¯¤˜ ÛÙË Û‡ÓıÂÛË ‹ ÛÙË ‰Ú¿ÛË Ù˘ GH ÌÔÚÔ‡Ó Ó· ÚÔηϤÛÔ˘Ó Ì›· ÌÂÁ¿ÏË ÔÈÎÈÏ›· ÛÙÔÓ
ÎÏÈÓÈÎfi Ê·ÈÓfiÙ˘Ô ÙˆÓ ·ÛıÂÓÒÓ. À¿Ú¯Ô˘Ó Ù¤ÛÛÂÚȘ ‰È·ÊÔÚÂÙÈÎÔ› Ù‡ÔÈ ÌÂÌÔӈ̤Ó˘ ·Ó¿ÚÎÂÈ·˜ ·˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘: Ô Ù‡Ô˜ π∞, πµ, ππ Î·È πππ. ∂ÈÚfiÛıÂÙ·, ¤Ó·˜ Û˘Ó¯Ҙ ·˘Í·ÓfiÌÂÓÔ˜ ·ÚÈıÌfi˜ ·ÛıÂÓÒÓ Ì ÔÏÏ·Ï‹ ˘ÔÊ˘Ûȷ΋ ·Ó¿ÚÎÂÈ·
¤¯ÂÈ ·Ó·ÊÂÚı› fiÙÈ ¤¯ÂÈ ÌÂÙ·ÏÏ¿ÍÂȘ ÛÙÔ˘˜ ·Ú¿-
ÁÔÓÙ˜ ÌÂÙ·ÁÚ·Ê‹˜ Ù˘ ˘fiÊ˘Û˘: Pit-1, Prop-1, LHX3 Î·È Hesx-1. ∞˘Ù¤˜ ÔÈ ‰È·Ù·Ú·¯¤˜ ÌÔÚÔ‡Ó Ó·
·Ú·ÙËÚËıÔ‡Ó Ì ‰È·ÊÔÚÂÙÈ΋ Û˘¯ÓfiÙËÙ· ÛÙÔ˘˜ ·ÛıÂÓ›˜. ∏ ¯Ú‹ÛË Ù˘ ÌÔÚȷ΋˜ ‚ÈÔÏÔÁ›·˜ Î·È Ù˘ ÁÂÓÂÙÈ΋˜ ÛÙË ‰È¿ÁÓˆÛË ·˘ÙÒÓ ÙˆÓ ·ı‹ÛˆÓ
ÌÔÚ› Ó· ÂÍ·ÛÊ·Ï›ÛÂÈ Ì›· ÈÔ ÛˆÛÙ‹ ÚÔÛ¤ÁÁÈÛË
ÛÙÔ˘˜ ıÂڷ¢ÙÈÎÔ‡˜ ¯ÂÈÚÈÛÌÔ‡˜.
§¤ÍÂȘ ÎÏÂȉȿ: ·Ó¿ÚÎÂÈ· ·˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘, ÁÔÓ›‰ÈÔ GH, Pit-1, Prop-1, LHX3
∂ÈÛ·ÁˆÁ‹ ∏ ·Ó¿ÚÎÂÈ· ·˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘ (Growth hormone deficiency) Â›Ó·È Ì›· ‰È·Ù·Ú·¯‹ Ô˘ ÂÌÊ·Ó›˙ÂÙ·È ·ÁÎÔÛÌ›ˆ˜ ÛÂ Û˘¯ÓfiÙËÙ· 1:4000-10000
∞’ ¶·È‰È·ÙÚÈ΋ ∫ÏÈÓÈ΋, ¡ÔÛÔÎÔÌÂ›Ô ¶·›‰ˆÓ “¶. & ∞. ∫˘ÚÈ·ÎÔ‡”, ∞ı‹Ó·
Abstract: Some non-organic causes for growth hormone deficiency (GHD) can be attributed to genetic defects within the hypothalamo-pituitary axis. Recent advances have led to the characterization of a number of genes which are directly involved in pituitary development and related functions. Micromutations within the growth hormone (GH) and GH-releasing hormone receptor gene (GHRH) have been detected as a cause of isolated GHD. The resulting abnormalities in the synthesis or the activity of GH can give rise to a wide variation in the clinical phenotype of the patient. Four different types of isolated GH deficiency (IGHD) have been described: type IA, type IB and types II and III. In addition, increasing numbers of patients with combined pituitary hormone deficiencies (CGHD) have been reported, presenting mutations within pituitary transcription factors Pit-1, Prop-1, LHX3 and Hesx-1. These various defects can be observed with different frequencies in clinical practice. The use of molecular and genetic diagnostic methods for certain cases of GH deficiency can provide the basis for a more accurate approach to therapeutic management. Key words: growth hormone deficiency (GHD), gene GH, Pit-1, Prop-1, LHX3
ÁÂÓÓ‹ÛÂȘ (1-3). ªfiÓÔ ÙÔ 20% ÙˆÓ ÂÚÈÙÒÛÂˆÓ ÔÊ›ÏÂÙ·È Û οÔÈÔ ÔÚÁ·ÓÈÎfi ·›ÙÈÔ (.¯. ÙÚ·‡Ì·, fiÁÎÔ ‹ Ïԛ̈ÍË), ÂÓÒ ÛÙȘ ˘fiÏÔȘ ÂÚÈÙÒÛÂȘ Ë ·ÈÙÈÔÏÔÁ›· Â›Ó·È ¿ÁÓˆÛÙË (Idiopathic) (4,5). ÕÚ·,
1st Pediatric Clinic, “P. & A. Kyriakou”Children’s Hospital, Athens
Ë È‰ÈÔ·ı‹˜ ·Ó¿ÚÎÂÈ· ·˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘ GH
(Idiopathic GHD) ÂÚÈÏ·Ì‚¿ÓÂÈ fiϘ ÙȘ ÎÏÈÓÈΤ˜
ÂÚÈÙÒÛÂȘ ·Ó¿ÚÎÂÈ·˜ ·˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘ ÁÈ·
ÙȘ Ôԛ˜ ‰ÂÓ ˘¿Ú¯ÂÈ ÂÌÊ·Ó‹˜ ·ÈÙ›· (6). ¶·Ú’ fiÏ·
·˘Ù¿, ÔÈ ·Ú·ÙËÚ‹ÛÂȘ ‰Â›¯ÓÔ˘Ó fiÙÈ ÙÔ 5-30% ·˘-
ÙÒÓ ÙˆÓ ÂÚÈÙÒÛÂˆÓ ¤¯ÂÈ Û˘ÁÁÂÓ›˜ ÚÒÙÔ˘ ‚·ı-
ÌÔ‡ Ì ·Ó·Ú΋ ۈ̷ÙÈ΋ ·Ó¿Ù˘ÍË, ÁÂÁÔÓfi˜
Ô˘ ÂÈÛËÌ·›ÓÂÈ fiÙÈ ÌÔÚ› Ó· ˘Ê›ÛÙ·Ù·È Ì›· Èı·-
Ó‹ ÁÂÓÂÙÈ΋ ‰È·Ù·Ú·¯‹ (7).
∏ ·Ó¿ÚÎÂÈ· Ù˘ ·˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘ ÌÔÚ›
Ó· Â›Ó·È ÌÂÌÔӈ̤ÓË (Isolated growth hormone deficiency, IGHD) ‹ Ó· Û˘Ó‰˘¿˙ÂÙ·È Ì ·Ó¿ÚÎÂÈ·
Î·È ¿ÏÏˆÓ ˘ÔÊ˘ÛÈ·ÎÒÓ ÔÚÌÔÓÒÓ (Multiple pituitary hormone deficiency, MPHD).
¶ÚfiÛÊ·Ù˜ ÂÈÛÙËÌÔÓÈΤ˜ ÚfiÔ‰ÔÈ, fiˆ˜ Ë
·Ó¿Ï˘ÛË D¡∞, ¤¯Ô˘Ó Ô‰ËÁ‹ÛÂÈ ÛÙËÓ Ù·˘ÙÔÔ›ËÛË
ÂÓfi˜ ·ÚÈıÌÔ‡ ÁÔÓȉ›ˆÓ, Ù· ÔÔ›· Â›Ó·È ·Â˘ı›·˜
ÂÌÏÂÎfiÌÂÓ· ÛÙËÓ ·Ó¿Ù˘ÍË Ù˘ ˘fiÊ˘Û˘ Î·È ÙȘ
ÂÍ·ÚÙÒÌÂÓ˜ ·fi ·˘Ù‹ ÏÂÈÙÔ˘ÚÁ›Â˜. ªÂÚÈο ÂÍ ·˘-
ÙÒÓ ¤¯Ô˘Ó ·ÔÌÔÓˆı› ·Â˘ı›·˜ ÛÙÔÓ ¿ÓıÚˆÔ, ÂÓÒ ¿ÏÏ· ¤¯Ô˘Ó Û˘Û¯ÂÙÈÛÙ› ·fi ÂÓÔ¯ÔÔ›ËÛË ÛÂ
ÌÔÓ٤Ϸ ·Ó·ÚÎÔ‡˜ ·Ó¿Ù˘Í˘ (8).
∞Ó¿Ù˘ÍË Ù˘ ˘fiÊ˘Û˘ ∏ ˘fiÊ˘ÛË ·ÔÙÂÏÂ›Ù·È ·fi ÙÔÓ ÚfiÛıÈÔ ÏÔ‚fi, Ô ÔÔ›Ô˜ ·ÔÙÂÏ› Î·È ÙÔ 75% ÙÔ˘ ‚¿ÚÔ˘˜ ÙÔ˘ ·‰¤-
Ó· Î·È ÚÔ¤Ú¯ÂÙ·È ·fi ÚÔÛÂ΂ÔÏ‹ ÙÔ˘ ¤Íˆ ‚Ï·-
ÛÙÈÎÔ‡ ‰¤ÚÌ·ÙÔ˜ (ı‡Ï·Î·˜ ÙÔ˘ Rantke) Î·È ·fi
ÙÔÓ Ô›ÛıÈÔ ÏÔ‚fi, Ô ÔÔ›Ô˜ ÚÔ¤Ú¯ÂÙ·È ·fi Ó¢ÚÈ-
ο ·ÙÙ·Ú· ÙÔ˘ ‰¿ÊÔ˘˜ Ù˘ 3˘ ÎÔÈÏ›·˜. OÈ ÔÚ-
ÌfiÓ˜ ÙÔ˘ ÚfiÛıÈÔ˘ ÏÔ‚Ô‡ Û˘ÓÙ›ıÂÓÙ·È ·fi ¤ÓÙÂ
‰È·ÊÔÚÂÙÈΤ˜ ÔÌ¿‰Â˜ ÂÎÎÚÈÙÈÎÒÓ Î˘ÙÙ¿ÚˆÓ (ۈ̷-
ÙÔÙÚfi·, ÁÔÓ·‰ÔÙÚfi·, Ï·ÎÙÔÙÚfi·, ı˘ÚÂÔÙÚfi·
Î·È ÎÔÚÙÈÎÔÙÚfi·), ˘fi ÙËÓ Â›‰Ú·ÛË ˘Ôı·Ï·ÌÈ-
ÎÒÓ ÔÚÌÔÓÒÓ. ∏ ÂͤÏÈÍË ÙˆÓ Î˘ÙÙ¿ÚˆÓ ·˘ÙÒÓ Î·Ù¿
ÙËÓ ·Ú¯¤ÁÔÓË ÂÌÊ¿ÓÈÛ‹ ÙÔ˘˜ Û˘Ì‚·›ÓÂÈ Û ·˘ÛÙË-
Ú‹ ¯ÚÔÓÈ΋ ÛÙÈÁÌ‹. ŒÙÛÈ, ÚÒÙ· ÌÔÚÔ‡Ó Ó· ·Ó·-
ÁÓˆÚÈÛÙÔ‡Ó Ù· ÎÔÚÙÈÎÔÙÚfi· ·ÙÙ·Ú·, ÛÙË Û˘Ó¤-
¯ÂÈ· Ù· ÁÔÓ·‰ÔÙÚfi· Î·È Ù· ı˘ÚÂÔÙÚfi· ηÈ, Ù¤ÏÔ˜, ÂÌÊ·Ó›˙ÔÓÙ·È Ù· ۈ̷ÙÔÏ·ÎÙÔÙÚfi· (somatolactotropes cells) Ô˘ Â›Ó·È Úfi‰ÚÔÌ· ·Ù-
Ù·Ú· ÙˆÓ ÛˆÌ·ÙÔÙÚfiˆÓ Î·È ÙˆÓ Ï·ÎÙÔÙÚfiˆÓ
΢ÙÙ¿ÚˆÓ. ∏ ‰È·ÊÔÚÔÔ›ËÛË Î·È Ô ÔÏÏ·Ï·ÛÈ·-
ÛÌfi˜ ÙˆÓ Î˘ÙÙ¿ÚˆÓ ·˘ÙÒÓ, Ô˘ Ï·Ì‚¿ÓÂÈ ¯ÒÚ·
ÛÙ· ÚÒÙ· ÛÙ¿‰È· Ù˘ ÂÌ‚Ú˘˚΋˜ ·Ó¿Ù˘Í˘ (12Ë15Ë ÂÌ‚Ú˘˚΋ Ë̤ڷ), ÙÂÏÂ›Ù·È ˘fi ÙËÓ Â›‰Ú·ÛË
ÔÚÈÛÌ¤ÓˆÓ ÚˆÙÂ˚ÓÒÓ (DNA-binding proteins), ÔÈ Ôԛ˜ ÔÓÔÌ¿˙ÔÓÙ·È ·Ú¿ÁÔÓÙ˜ ÌÂÙ·ÁÚ·Ê‹˜ (Homeodomain containing transcription factors) (5,8-10).
¶·Ú¿ÁÔÓÙ˜ ÌÂÙ·ÁÚ·Ê‹˜ (Transcription factors)
∆· ÁÔÓ›‰È·, ÂÎÙfi˜ ·fi ÙËÓ ÏËÚÔÊÔÚ›· ÁÈ· ÙË ‰ÔÌ‹ Ù˘ ÚˆÙ½Ó˘, ÙËÓ ÔÔ›· Έ‰ÈÎÔÔÈÔ‡Ó (‰ÔÌÈ΋
ÂÚÈÔ¯‹ ÙÔ˘ ÁÔÓȉ›Ô˘), ÂÚȤ¯Ô˘Ó Î·È ÙËÓ ÏËÚÔÊÔÚ›· ÁÈ· ÙË Ú‡ıÌÈÛË Ù˘ ›‰È·˜ ÙÔ˘˜ Ù˘ ¤ÎÊÚ·Û˘ (Ú˘ıÌÈÛÙÈ΋ ÂÚÈÔ¯‹). OÈ ·ÏÏËÏÔ˘¯›Â˜ Ô˘ ÂÓ¤¯ÔÓÙ·È ÛÙË Ú‡ıÌÈÛË Ù˘ ÁÔÓȉȷ΋˜ ¤ÎÊÚ·Û˘ ‰È·ÎÚ›ÓÔÓÙ·È Û ‰‡Ô ηÙËÁÔڛ˜: Ë Ì›· ÂÚÈÔ¯‹ Ô˘ ‚Ú›ÛÎÂÙ·È ÎÔÓÙ¿ ÛÙÔ ÛËÌÂ›Ô ¤Ó·Ú͢ Ù˘ ÌÂÙ·ÁÚ·Ê‹˜ ϤÁÂÙ·È ˘ÔÎÈÓËÙ‹˜ (Promoter) Î·È Ë ¿ÏÏË Ï¤ÁÂÙ·È ÂÓÈÛ¯˘Ù‹˜ (Enhancer). ™ÙËÓ ÂÚÈÔ¯‹ ÙÔ˘ ˘ÔÎÈÓËÙ‹ ˘¿Ú¯Ô˘Ó
ηıÔÚÈṲ̂Ó˜ ı¤ÛÂȘ, ÛÙȘ Ôԛ˜ ÚÔÛ‰¤ÓÔÓÙ·È Û˘ÁÎÂÎÚÈ̤Ó˜ Ú˘ıÌÈÛÙÈΤ˜ ÚˆÙ½Ó˜, ÔÈ ·Ú¿ÁÔÓÙ˜ ÌÂÙ·ÁÚ·Ê‹˜ (Transcription factors), ÁÈ· ÙË Ú‡ıÌÈÛË Ù˘ ÁÔÓȉȷ΋˜ ¤ÎÊÚ·Û˘.
™ÙË ‰È·‰Èηۛ· ÌÂÙ·ÁÚ·Ê‹˜ ÙÔ˘ DNA Û RNA Û˘ÌÌÂÙ¤¯Ô˘Ó ÔÈ RNA-ÔÏ˘ÌÂÚ¿Û˜ (π, ππ Î·È πππ). ∞fi ·˘Ù¤˜, Ë RNA ÔÏ˘ÌÂÚ¿ÛË II, ·Ó·ÁÓˆÚ›˙ÂÈ ÛÙËÓ ÂÚÈÔ¯‹ ÙÔ˘ ˘ÔÎÈÓËÙ‹ Û˘ÁÎÂÎÚÈ̤Ó˜ ·ÏÏËÏÔ˘¯›Â˜ (˙‡ÁË ‚¿ÛˆÓ), ÛÙȘ Ôԛ˜ Î·È ÚÔÛ‰¤ÓÂÙ·È. °È· ÙËÓ ¤Ó·ÚÍË, fï˜, Ù˘ ÌÂÙ·ÁÚ·Ê‹˜ ¯ÚÂÈ¿˙ÂÙ·È Ó· Û˘Ó‰ÂıÔ‡Ó ÛÙÔ DNA Î·È ¿ÏϘ ÚˆÙ½Ó˜, ÔÈ Ôԛ˜ Â›Ó·È ÔÈ ÁÓˆÛÙÔ› ·Ú¿ÁÔÓÙ˜ ÌÂÙ·ÁÚ·Ê‹˜ (Transcription factors). OÈ ·Ú¿ÁÔÓÙ˜ ÌÂÙ·ÁÚ·Ê‹˜, ‰ËÏ·‰‹, Â›Ó·È Ô “ÌÔÚÈ·Îfi˜ ‰È·ÎfiÙ˘” - Ë ··Ú¯‹ - Ô˘ ÌÔÚ› Ó· ‰ÈÂÁ›ÚÂÈ ‹ Ó· ηٷÛÙ›ÏÂÈ ÙËÓ ¤ÎÊÚ·ÛË ÂÓfi˜ ÁÔÓȉ›Ô˘ (11,12).
°ÔÓ›‰È· Ô˘ ÂÓ¤¯ÔÓÙ·È ÛÙÔ Û¯ËÌ·ÙÈÛÌfi Î·È ÙË
ÏÂÈÙÔ˘ÚÁ›· ÙÔ˘ ÚfiÛıÈÔ˘ ÏÔ‚Ô‡-˘fiÊ˘Û˘ ·) °ÔÓ›‰ÈÔ Ù˘ ·˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘ (GHI): Έ‰ÈÎÔÔÈ› ÙËÓ ÂÓÙÔÏ‹ ÁÈ· ÙË Û‡ÓıÂÛË Ù˘ ˘ÔÊ˘Ûȷ΋˜ GH.
‚) °ÔÓ›‰ÈÔ ÙÔ˘ GHRHR: Έ‰ÈÎÔÔÈ› ÙÔÓ ˘Ô‰Ô¯¤·, Ì ÙÔÓ ÔÔ›Ô Û˘Ó‰¤ÂÙ·È Ô ·Ú¿ÁÔÓÙ·˜ ¤ÎÏ˘Û˘ Ù˘ ·˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘ (Growth hormone releasing hormone-GHRH) Î·È ‰ÈÂÁ›ÚÂÈ ÙËÓ ¤ÎÎÚÈÛË GH.
Á) °ÔÓ›‰È· POUIF-1, Prop-1, LHX3, Hesx-1: Â›Ó·È “ÔÌÔÈÔÙÈο” ÁÔÓ›‰È· (homeobox genes), Ù· ÔÔ›· Έ‰ÈÎÔÔÈÔ‡Ó Ì›· ÔÈÎÔÁ¤ÓÂÈ· ·Ú·ÁfiÓÙˆÓ ÌÂÙ·ÁÚ·Ê‹˜ (transcription factors), ÔÈ ÔÔ›ÔÈ ÂÓ¤¯ÔÓÙ·È ÛÙËÓ ÔÚÁ·ÓÔÁ¤ÓÂÛË ÙÔ˘ ÚfiÛıÈÔ˘ ÏÔ‚Ô‡ Ù˘ ˘fiÊ˘Û˘ Î·È ÛÙË Ú‡ıÌÈÛË Ù˘ ¤ÎÎÚÈÛ˘ GH.
ªÂÙ·ÏÏ¿ÍÂȘ Û fiÏ· ·˘Ù¿ Ù· ÁÔÓ›‰È· ¤¯Ô˘Ó ˘¿ÚÍÂÈ Î·È ÂÎÊÚ¿˙ÔÓÙ·È Ì ·Ó¿ÚÎÂÈ· Ù˘ GH ‹ Î·È ¿ÏÏˆÓ ÔÚÌÔÓÒÓ (6,8,13).
¢È·Ù·Ú·¯¤˜ ÛÙÔ ÁÔÓ›‰ÈÔ Ù˘ GH
∆o ÁÔÓ›‰ÈÔ GH1, Ô˘ Â›Ó·È ˘Â‡ı˘ÓÔ ÁÈ· ÙË Û‡ÓıÂÛË Ù˘ ·˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘, Â›Ó·È ¤Ó· ·fi Ù· ÚÒÙ· ·ÓıÚÒÈÓ· ÁÔÓ›‰È· Ô˘ Ù·˘ÙÔÔÈ‹ıËÎ·Ó Î·È Â‰Ú¿˙ÂÙ·È ÛÙÔ ·ÓıÚÒÈÓÔ ¯ÚˆÌfiۈ̷ 17q23 (8,14). OÈ ÚÒÙ˜ ÌÔÚȷΤ˜ ‰È·Ù·Ú·¯¤˜ ÙÔ˘ ÁÔÓȉ›Ô˘ GH1 ·Ó·Î·Ï‡ÊıËÎ·Ó ÚÈÓ ·fi 20 ÂÚ›Ô˘ ¯ÚfiÓÈ· ·fi ÙÔÓ John Phillips Î·È ¯·Ú·ÎÙËÚ›ÛÙËÎ·Ó ˆ˜ ·ÒÏÂȘ ÙÌ‹Ì·ÙÔ˜ (deletion) ÙÔ˘ ÁfiÓÔ˘ Ù˘ GH
(15). ÀÔÏÔÁ›˙ÂÙ·È fiÙÈ ÂÚ›Ô˘ ÙÔ 13-15% ÙˆÓ ·ÛıÂÓÒÓ Ì ÛÔ‚·Ú‹ ÌÂÌÔӈ̤ÓË ·Ó¿ÚÎÂÈ· ·˘-
ÍËÙÈ΋˜ ÔÚÌfiÓ˘ (>-4,5 SD ÛÙÔ ‡„Ô˜) ¤¯ÂÈ ·˘ÙÔ‡
ÙÔ˘ ›‰Ô˘˜ ÙË ÌÂÙ¿ÏÏ·ÍË ÛÙÔ ÁÔÓ›‰ÈÔ GH1 (16,17).
∞ÚÁfiÙÂÚ·, ·Ú·ÙËÚ‹ıËÎ·Ó Î·È ¿ÏϘ ‰È·Ù·Ú·-
¯¤˜ ÛÙÔ ÁÔÓ›‰ÈÔ Ù˘ GH, Ô˘ Û¯ÂÙ›˙ÔÓÙ·È Ì ÙË Û‡Ó-
ıÂÛË Î·È ÙË ‰Ú·ÛÙËÚÈfiÙËÙ· Ù˘ GH Î·È ÔÈ Ôԛ˜
ÌÔÚ› Ó· Â›Ó·È ˘Â‡ı˘Ó˜ ÁÈ· ÙÔ˘˜ ‰È¿ÊÔÚÔ˘˜ ÎÏÈÓÈÎÔ‡˜ Ê·ÈÓfiÙ˘Ô˘˜ ÙˆÓ ·ÛıÂÓÒÓ Ì ·Ó¿ÚÎÂÈ· ·˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘. Œ¯Ô˘Ó ÂÚÈÁÚ¿ÊÂÈ Ù¤ÛÛÂÚȘ ÔÈÎÔÁÂÓ›˜ Ù‡ÔÈ ÌÂÌÔӈ̤Ó˘ ·Ó¿ÚÎÂÈ·˜ ·˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘. OÈ ‰‡Ô ÎÏËÚÔÓÔÌÔ‡ÓÙ·È Ì ˘ÔÏÂÈfiÌÂÓÔ ÛˆÌ·ÙÈÎfi ¯·Ú·ÎÙ‹Ú· (IGHD πA Î·È πµ), ¤Ó·˜ Ì ÂÈÎÚ·ÙÔ‡ÓÙ· (IGHD II) Î·È Ô Ù¤Ù·ÚÙÔ˜ ÌÂ
Ê˘ÏÔÛ‡Ó‰ÂÙÔ (IGHD IIπ) (16).
™ÙÔÓ ÚÒÙÔ Ù‡Ô π∞ Ù˘ ÌÂÌÔӈ̤Ó˘ ·Ó¿Ú-
ÎÂÈ·˜ ·˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘, ÔÈ ‰È·Ù·Ú·¯¤˜ (defects)
ÛÙÔ ÁÔÓ›‰ÈÔ GH1 ·ÊÔÚÔ‡Ó Â›Ù Û ·ÒÏÂÈ· ÌÂÁ¿-
ÏÔ˘ ·ÚÈıÌÔ‡ ‚¿ÛÂˆÓ (deletion) ‹ Û ÌÂÙ·ÏÏ¿ÍÂȘ
Ô˘ ÚÔηÏÔ‡Ó ‰È·Ù·Ú·¯‹ ÙÔ˘ Ï·ÈÛ›Ô˘ ·Ó¿ÁÓˆÛ˘ (frame-shift mutation) ‹ Û ÌÂÙ·ÏÏ¿ÍÂȘ fiÔ˘
˘¿Ú¯ÂÈ ÌÂÙ·ÙÚÔ‹ ÂÓfi˜ ·ÌÈÓÔͤԘ Û Έ‰ÈÎfiÓÈÔ
Ï‹Í˘, ·ÓÂÚÌËÓ‡ÛÈÌË ÌÂÙ¿ÏÏ·ÍË (nonsense mutation) (16,18-20). OÈ ·ÛıÂÓ›˜ Ô˘ ·Ó‹ÎÔ˘Ó ÛÂ
·˘ÙfiÓ ÙÔÓ Ù‡Ô ·Ó¿ÚÎÂÈ·˜ ·˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘ ·Ó·ÏÔÁÔ‡Ó ÂÚ›Ô˘ ÛÙÔ 10% ÙˆÓ ·ÛıÂÓÒÓ Ì ÌÂÌÔӈ̤ÓË ·Ó¿ÚÎÂÈ· ·˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘ (21) ηÈ
¤¯Ô˘Ó Û˘Ó‹ıˆ˜ Ôχ ÎÔÓÙfi ·Ó¿ÛÙËÌ·, Ï‹ÚË ¤ÏÏÂÈ„Ë ·˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘ Î·È ÙȘ ÂÚÈÛÛfiÙÂÚ˜ ÊÔÚ¤˜, fiÙ·Ó ÙÔ˘˜ ¯ÔÚËÁÂ›Ù·È GH, ·Ú¿ÁÔ˘Ó ·ÓÙÈÛÒÌ·Ù· ¤Ó·ÓÙÈ ·˘Ù‹˜.
™ÙÔÓ Ù‡Ô IGHD πµ, ÔÈ ÌÂÙ·ÏÏ¿ÍÂȘ ÙÔ˘ ÁÔÓ›‰ÈÔ˘ GH ·ÊÔÚÔ‡Ó Û ˘ÔηٷÛÙ¿ÛÂȘ ‚¿ÛÂˆÓ Ô˘ ÂËÚ¿˙Ô˘Ó ÙË ‰È·‰Èηۛ· Ù˘ ·ÔÎÔ‹˜ Î·È Ù˘ Â·Ó·Û˘ÁÎfiÏÏËÛ˘ (splicing) ÙÔ˘ RNA (16). OÈ ·ÛıÂÓ›˜ Ô˘ ·Ó‹ÎÔ˘Ó Û ·˘ÙfiÓ ÙÔÓ Ù‡Ô ¤¯Ô˘Ó ¯·ÌËϤ˜ ÙÈ̤˜ ·˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘, ηϋ ·ÓÙ·fiÎÚÈÛË Û ıÂڷ›· ˘ÔηٿÛÙ·Û˘ Ì GH Î·È ‰ÂÓ ·Ó·Ù‡ÛÛÔ˘Ó ·ÓÙÈÛÒÌ·Ù· ¤Ó·ÓÙÈ ·˘Ù‹˜ (16,18). ™ÙÔÓ Ù‡Ô IGHD ππ, ÔÈ ÌÂÙ·ÏÏ¿ÍÂȘ ÛÙÔ ÁÔÓ›‰ÈÔ Ù˘ GH ·ÊÔÚÔ‡Ó - Î·È Û ·˘Ù‹ ÙËÓ ÂÚ›ÙˆÛË - Û ˘ÔηٷÛÙ¿ÛÂȘ ‹ ·ÒÏÂȘ ‚¿ÛÂˆÓ Ô˘ ÂËÚ¿˙Ô˘Ó ÙË ‰È·‰Èηۛ· Ù˘ ·ÔÎÔ‹˜ ÙˆÓ ÈÓÙÚÔÓ›ˆÓ Î·È Ù˘ ¤ÓˆÛ˘ ÙˆÓ Â͈ӛˆÓ (Ì¿ÙÈÛÌ·-splicing) ÙÔ˘ RNA (splice site mutation) (16,22-24). OÈ ·ÛıÂÓ›˜ Ì ·Ó¿ÚÎÂÈ· ·˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘, Ô˘ ·Ó‹ÎÔ˘Ó ÛÙÔÓ Ù‡Ô IGHD II, ¤¯Ô˘Ó Î·È ·˘ÙÔ› ÎÔÓÙfi ·Ó¿ÛÙËÌ·, ¯·ÌËϤ˜ ÙÈ̤˜ GH, ηϋ ·ÓÙ·fiÎÚÈÛË ÛÙË ıÂڷ›· ˘ÔηٿÛÙ·Û˘ Î·È ‰ÂÓ ·Ó·Ù‡ÛÛÔ˘Ó ·ÓÙÈÛÒÌ·Ù· ¤Ó·ÓÙÈ Ù˘ GH.
∆¤ÏÔ˜, ÔÈ ·ÛıÂÓ›˜ Ô˘ ·Ó‹ÎÔ˘Ó ÛÙÔÓ Ù‡Ô IGHD III ·ÚÔ˘ÛÈ¿˙Ô˘Ó ¤ÏÏÂÈ„Ë Ù˘ ·˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘, ÂÓÒ ÌÂÚÈÎÔ› ·fi ·˘ÙÔ‡˜ ¤¯Ô˘Ó Î·È ·Á·ÌÌ·ÛÊ·ÈÚÈÓ·ÈÌ›· (25). OÈ ÌÔÚȷΤ˜ ‰È·Ù·Ú·¯¤˜ Ô˘
ÛÙÔ ÁÔÓ›‰ÈÔ Ù˘ GH Û ·˘Ù¤˜ ÙȘ ÂÚÈÙÒÛÂȘ, ‰ÂÓ Â›Ó·È Ï‹Úˆ˜ ÁÓˆÛÙ¤˜ (26,27).
ªÂÙ·ÏÏ¿ÍÂȘ ÛÙÔ ÁÔÓ›‰ÈÔ ÙÔ˘ ˘Ô‰Ô¯¤· GHRH
™ÙÔÓ ÚfiÛıÈÔ ÏÔ‚fi Ù˘ ˘fiÊ˘Û˘, ÛÙ· ۈ̷ÙÔÙÚfi· ·ÙÙ·Ú·, ÙÔ ˘Ôı·Ï·ÌÈÎfi ÂÚ¤ıÈÛÌ· ÁÈ· ÙÔÓ
·Ú¿ÁÔÓÙ· ¤ÎÏ˘Û˘ Ù˘ ·˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘ (Growth hormone releasing hormone, GHRH) ·Ó·ÁÓˆÚ›˙ÂÙ·È
Î·È ÌÂٷʤÚÂÙ·È ·fi ¤Ó·Ó ÂȉÈÎfi GHRH ˘Ô‰Ô¯¤· (receptor). O GHRHR ·Ó‹ÎÂÈ ÛÙËÓ ÔÈÎÔÁ¤ÓÂÈ· ÙˆÓ ˘Ô‰Ô¯¤ˆÓ Ô˘ Û˘Ó‰¤ÔÓÙ·È Ì ÙÔ Û‡ÛÙËÌ· ÙˆÓ GÚˆÙÂ˚ÓÒÓ (G-protein coupled receptors). ∆Ô Û‡ÛÙËÌ· ÙˆÓ G-ÚˆÙÂ˚ÓÒÓ ·ÔÙÂÏ› ¤Ó· ‰È¿ÌÂÛÔ ·Ú¿ÁÔÓÙ· Ô˘ ÌÂٷʤÚÂÈ ÙÔ ·Ú¯ÈÎfi ÂÚ¤ıÈÛÌ· ·fi ÙÔÓ ˘Ô‰Ô¯¤· ÚÔ˜ ÙÔ ÂÓ˙˘ÌÈÎfi Û‡ÛÙËÌ· Ô˘ ·Ú¿ÁÂÈ ÙÔÓ “‰Â‡ÙÂÚÔ ·ÁÁÂÏÈÔÊfiÚÔ” (28).
∆o ÁÔÓ›‰ÈÔ ÙÔ˘ GHRHR Ù·˘ÙÔÔÈ‹ıËΠÙÔ 1992 Î·È Â‰Ú¿˙ÂÙ·È ÛÙÔ 7Ú ·ÓıÚÒÈÓÔ ¯ÚˆÌfiۈ̷ (29).
O GHRH ˘Ô‰Ô¯¤·˜ ¤¯ÂÈ ¤Ó· ÛËÌ·ÓÙÈÎfi ÚfiÏÔ
ÛÙÔÓ ÔÏÏ·Ï·ÛÈ·ÛÌfi Î·È ÛÙË ‰È·ÊÔÚÔÔ›ËÛË ÙˆÓ ÛˆÌ·ÙÔÙÚfiˆÓ ΢ÙÙ¿ÚˆÓ Ù˘ ˘fiÊ˘Û˘ ηÈ
ÙËÓ ÈηÓfiÙËÙ¿ ÙÔ˘˜ Ó· ·Ú¿ÁÔ˘Ó ·˘ÍËÙÈ΋ ÔÚÌfiÓË (30).
¯ÚfiÓÈ· ¤¯Ô˘Ó ·Ó·ÊÂÚı› ‰È·Ù·Ú·¯¤˜ ÙÔ˘ ÁÔÓ›‰ÈÔ˘ GHRHR, ÔÈ Ôԛ˜ ·ÊÔÚÔ‡Ó ÛÙË ÌÂÙ·ÙÚÔ‹ ÂÓfi˜ ·ÌÈÓÔͤԘ Û Έ‰ÈÎfiÓÈÔ Ï‹Í˘, ·ÓÂÚÌËÓ‡ÛÈÌË ÌÂÙ¿ÏÏ·ÍË (nonsense mutation) ‹ ÌÂÙ·ÏÏ¿ÍÂȘ Ô˘ ·ÊÔÚÔ‡Ó Û ˘ÔηٷÛÙ¿ÛÂȘ ‚¿ÛÂˆÓ Î·È ÂËÚ¿˙Ô˘Ó ÙË ‰È·‰Èηۛ· Ù˘ ·ÔÎÔ‹˜ Î·È Ù˘ Â·Ó·Û˘ÁÎfiÏÏËÛ˘ (splicing) ÙÔ˘ RNA (splice site mutation) (31-37). ŸÏ˜ ·˘Ù¤˜ ÔÈ ‰È·Ù·Ú·¯¤˜ ÌÂÙ·‚È‚¿˙ÔÓÙ·È Ì ˘ÔÏÂÈfiÌÂÓÔ ¯·Ú·ÎÙ‹Ú·.
OÈ ·ÛıÂÓ›˜ Ì ÌÂÙ·ÏÏ¿ÍÂȘ ÛÙÔ GHRHR ÁÔÓ›‰ÈÔ ·ÚÔ˘ÛÈ¿˙Ô˘Ó ÛÔ‚·Ú‹ ·Ó¿ÚÎÂÈ· GH (¯ˆÚ›˜ ¤ÏÏÂÈ„Ë ¿ÏÏˆÓ ˘ÔÊ˘ÛÈ·ÎÒÓ ÔÚÌÔÓÒÓ) Î·È ˘ÔÏ·Û›· ÙÔ˘ ÚfiÛıÈÔ˘ ÏÔ‚Ô‡ Ù˘ ˘fiÊ˘Û˘, ÂÓÒ
¤¯Ô˘Ó ηϋ ·ÓÙ·fiÎÚÈÛË ÛÙË ıÂڷ›· ˘ÔηٿÛÙ·Û˘ Ì GH.
°ÔÓ›‰ÈÔ POUIF-1 (Pit-1) Î·È ÌÂÙ·ÏÏ¿ÍÂȘ
∆Ô ÁÔÓ›‰ÈÔ Pit-1 (Ë Â›ÛËÌË ÔÓÔÌ·Û›· ÙÔ˘ ÔÔ›Ô˘, Û‹ÌÂÚ·, Â›Ó·È POUIF-1) Â›Ó·È ¤Ó· ̤ÏÔ˜ Ù˘ ÔÈÎÔÁ¤ÓÂÈ·˜ (POU) ÙˆÓ ·Ú·ÁfiÓÙˆÓ ÌÂÙ·ÁÚ·Ê‹˜ Î·È Â›Ó·È ˘Â‡ı˘ÓÔ ÁÈ· ÙËÓ ·Ó¿Ù˘ÍË Ù˘ ˘fiÊ˘Û˘ (38). O POUπF-1 Ù·˘ÙÔÔÈ‹ıËΠÁÈ· ÚÒÙË ÊÔÚ¿ ÙÔ 1988 (39) Î·È ‚Ú¤ıËΠfiÙÈ ÂÓÙÔ›˙ÂÙ·È ÛÙÔ 3ƒ11 ·ÓıÚÒÈÓÔ ¯ÚˆÌfiۈ̷ (40). ∏ Pit (1) ÚˆÙ½ÓË ·ÓȯÓ‡ÂÙ·È ÛÙÔÓ ˘Ú‹Ó· ÙÚÈÒÓ Î˘ÙÙ·ÚÈÎÒÓ ÛÂÈÚÒÓ ÙÔ˘ ÚfiÛıÈÔ˘ ÏÔ‚Ô‡ Ù˘ ˘fiÊ˘Û˘, ÙˆÓ ÛˆÌ·ÙÔÙÚfiˆÓ, ÙˆÓ Ï·ÎÙÔÙÚfiˆÓ Î·È ÙˆÓ ı˘ÚÂÔÂȉÔÙÚfiˆÓ (41,42). ø˜ ÂÎ ÙÔ‡ÙÔ˘, Ô ·Ú¿ÁˆÓ Pit
··Ú·›ÙËÙÔ˜ ·ÊÂÓfi˜ ÁÈ· ÙËÓ ·Ú¯È΋ ÂÌÊ¿ÓÈÛË ·˘ÙÒÓ ÙˆÓ Î˘ÙÙ·ÚÈÎÒÓ ÛÂÈÚÒÓ, ·ÊÂÙ¤ÚÔ˘ ÁÈ· ÙË ÌÂÙ¤ÂÈÙ· ‰È¤ÁÂÚÛ‹ ÙÔ˘˜.
ªÂÙ·ÏÏ¿ÍÂȘ, ÂÔ̤ӈ˜, ÛÙÔ POUIF-1 ÁÔÓ›‰ÈÔ
ÚÔηÏÔ‡Ó Û˘Ó‰˘·Ṳ̂ÓË ·Ó¿ÚÎÂÈ· ˘fiÊ˘Û˘
ÁÈ· ·˘ÍËÙÈ΋ ÔÚÌfiÓË (GH), ÚÔÏ·ÎÙ›ÓË (PRL) ηÈ
ı˘ÚÂÔÙÚfiÔ ÔÚÌfiÓË (TSH). ∏ ÚÒÙË ·ÓıÚÒÈÓË
ÌÂÙ¿ÏÏ·ÍË ÛÙÔ POUIF-1 ÁÔÓ›‰ÈÔ ·Ó·Ê¤ÚıËΠÙÔ
1992, Û ·È‰› ÌÂ Û˘Ó‰˘·Ṳ̂ÓË ·Ó¿ÚÎÂÈ· Ù˘
·˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘ Î·È Ù˘ ÚÔÏ·ÎÙ›Ó˘ (PRL) (43). ∏ ‰È·Ù·Ú·¯‹ ÔÚÌÔÓÒÓ Ô˘ ÔÊ›ÏÂÙ·È Û ÌÂ-
Ù¿ÏÏ·ÍË ÙÔ˘ POUIF-1 ÁÔÓȉ›Ô˘, ÌÂÙ·‚È‚¿˙ÂÙ·È Î˘-
Ú›ˆ˜ Ì ÙÔÓ ˘ÔÏÂÈfiÌÂÓÔ ¯·Ú·ÎÙ‹Ú· (43-49).
À¿Ú¯ÂÈ fï˜ Î·È ‰È·Ù·Ú·¯‹ Ô˘ ÌÂÙ·‰›‰ÂÙ·È ÌÂ
ÙÔÓ ÂÈÎÚ·ÙÔ‡ÓÙ· ¯·Ú·ÎÙ‹Ú·, ·Ó¿ÏÔÁ· ÌÂ ÙË ı¤ÛË
Ù˘ ÌÂÙ¿ÏÏ·Í˘ ÛÙÔ ÁÔÓ›‰ÈÔ (38,50-53).
∆· ›‰Ë ÙˆÓ ÌÂÙ·ÏÏ¿ÍÂˆÓ Ô˘ ¤¯Ô˘Ó ·Ó·ÊÂÚı› ̤¯ÚÈ Û‹ÌÂÚ· ÛÙÔ POUIF-1 ÁÔÓ›‰ÈÔ, Â›Ó·È ‰Ò‰Âη (54). ∆· ÂÓÓ¤· ·ÊÔÚÔ‡Ó Û ·ÚÂÚÌËÓ‡ÛÈ̘ ÌÂÙ·ÏÏ¿ÍÂȘ (missence mutation) (45,47,48, 50-53), Ù· ‰‡Ô Û ·ÓÂÚÌËÓ‡ÛÈ̘ (nonsense mutation) (43,46,47) Î·È ÙÔ ¤Ó· Û ¤ÏÏÂÈÌÌ· ‚¿ÛÂˆÓ (deletion) (44).
O Ê·ÈÓfiÙ˘Ô˜ ÙˆÓ ·ÛıÂÓÒÓ Ì ÌÂÙ·ÏÏ¿ÍÂȘ ÛÙÔ
ÁÔÓ›‰ÈÔ POUIF-1 ÔÈΛÏÏÂÈ Î·È ‰ÂÓ ¤¯ÂÈ Û¯¤ÛË Ì ÙÔ
›‰Ô˜ ÙˆÓ ÌÂÙ·ÏϿ͈Ó, Ô‡Ù Ì ÙÔÓ ÙÚfiÔ Ô˘
·˘Ù¤˜ ÎÏËÚÔÓÔÌÔ‡ÓÙ·È. ŸÏÔÈ ÔÈ ·ÛıÂÓ›˜ ¤¯Ô˘Ó ¤Ï-
ÏÂÈ„Ë GH, PRL Î·È TSH (9). ªÂÚÈÎÔ› ·fi ·˘ÙÔ‡˜
¤¯Ô˘Ó ˘Ôı˘ÚÂÔÂȉÈÛÌfi, ·ÚÎÂÙfi ¯ÚÔÓÈÎfi ‰È¿ÛÙËÌ·
ÚÈÓ ÂÌÊ·ÓÈÛÙ› Ë ¤ÏÏÂÈ„Ë ·˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘, ÂÓÒ
Û ¿ÏÏÔ˘˜ ·ÛıÂÓ›˜ ·ÚÔ˘ÛÈ¿˙ÂÙ·È ÌÂÙ¿ ÙËÓ ¤Ó·Ú-
ÍË Ù˘ ıÂڷ›·˜ Ì GH (55).
OÈ ·ÛıÂÓ›˜ Ì ÌÂÙ·ÏÏ¿ÍÂȘ ÛÙÔ POUIF-1 ÁÔÓ›‰ÈÔ ‰Â›¯ÓÔ˘Ó Ó· ÛÙÂÚÔ‡ÓÙ·È ÙËÓ ÂͤÏÈÍË ÙˆÓ ÛˆÌ·-
ÙÔÙÚfiˆÓ, ÙˆÓ Ï·ÎÙÔÙÚfiˆÓ Î·È ÙˆÓ ı˘ÚÂÔÂȉÔ-
ÙÚfiˆÓ ΢ÙÙ¿ÚˆÓ Ù˘ ˘fiÊ˘Û˘ Î·È ÁÈ’ ·˘Ùfi ¯ÚÂÈ-
¿˙ÔÓÙ·È ıÂڷ›· ˘ÔηٿÛÙ·Û˘.
°ÔÓ›‰ÈÔ Prop-1 Î·È ÌÂÙ·ÏÏ¿ÍÂȘ
∆o Prop-1 ÁÔÓ›‰ÈÔ Îˆ‰ÈÎÔÔÈ› ¤Ó·Ó ·Ú¿ÁÔÓÙ·
ÌÂÙ·ÁÚ·Ê‹˜ Ô˘ ÂÚÈÏ·Ì‚¿ÓÂÈ “ÔÌÔÈÔÂÚÈÔ¯‹” (homeodomain containing transcription factor) ηÈ
ıˆÚÂ›Ù·È Ô˘ÛÈ·ÛÙÈÎfi ÁÈ· ÙËÓ ¤ÎÊÚ·ÛË Ù˘ Pit
ÚˆÙ½Ó˘ ÛÙ· ۈ̷ÙÔÙÚfi·, Ï·ÎÙÔÙÚfi· Î·È ı˘-
ÚÂÔÂȉÔÙÚfi· ·ÙÙ·Ú· ÙÔ˘ ÚfiÛıÈÔ˘ ÏÔ‚Ô‡ Ù˘
˘fiÊ˘Û˘. ∏ ¤ÎÊÚ·Û‹ ÙÔ˘ Á›ÓÂÙ·È Î·Ù¿ ÙË ‰È¿ÚÎÂÈ· Ù˘ ÂÌ‚Ú˘˚΋˜ ·Ó¿Ù˘Í˘ Ù˘ ˘fiÊ˘Û˘ ηÈ
ÚÔËÁÂ›Ù·È ¿ÓÙÔÙ Ù˘ ¤ÎÊÚ·Û˘ ÙÔ˘ Pit ÁÔÓ›‰ÈÔ˘. °È’ ·˘Ùfi ÙÔ ÏfiÁÔ, ÔÓÔÌ¿˙ÂÙ·È Î·È ÚÔÊ‹Ù˘ ÙÔ˘ Pit (Prophet of Pit) (8,56,57).
∆Ô ÁÔÓ›‰ÈÔ Prop-1 ÛÙÔÓ ¿ÓıÚˆÔ Â‰Ú¿˙ÂÙ·È ÛÙÔ
¯ÚˆÌfiۈ̷ 5 (5q35) (58). ∏ ÚÒÙË ·ÓıÚÒÈÓË ÌÂ-
Ù¿ÏÏ·ÍË ÛÙÔ Prop-1 ÁÔÓ›‰ÈÔ ·Ó·Ê¤ÚıËΠÙÔ 1998
Î·È ·fi ÙfiÙ ¤¯Ô˘Ó ·Ó·ÊÂÚı› ÂÙ¿ ·ÎfiÌ· ÌÂÙ·Ï-
Ï¿ÍÂȘ (8). ŸÏ˜ ÔÈ ÌÂÙ·ÏÏ¿ÍÂȘ ÎÏËÚÔÓÔÌÔ‡ÓÙ·È Ì ˘ÔÏÂÈfiÌÂÓÔ ¯·Ú·ÎÙ‹Ú· Î·È ÔÈ
ÏÔ‡Ó ‰È·Ù·Ú·¯‹ ÙÔ˘ Ï·ÈÛ›Ô˘ ·Ó¿ÁÓˆÛ˘ (frameshift mutation) (59,60) ‹ ·ÏÏ·Á‹ Έ‰ÈÎÔÓ›Ô˘
ÛÙÔ mRNA ηÈ, ÂÔ̤ӈ˜, Ï¿ıÔ˜ ·ÌÈÓÔ͇ ÛÙËÓ ÔÏ˘ÂÙȉÈ΋ ·Ï˘Û›‰· ηٿ ÙË ÌÂÙ¿ÊÚ·ÛË-·ÚÂÚÌËÓ‡ÛÈ̘ ÌÂÙ·ÏÏ¿ÍÂȘ (missence mutation) (58,59,61) ‹ ÚÔηÏÔ‡Ó ·ÓÂÚÌËÓ‡ÛÈ̘ ÌÂÙ·ÏÏ¿ÍÂȘ (nonsense mutation) (8). O Ê·ÈÓfiÙ˘Ô˜ ÙˆÓ ·ÛıÂÓÒÓ ·˘ÙÒÓ ÔÈΛÏÏÂÈ, ÂÓÒ Ë ËÏÈΛ· Ù˘ ‰È¿ÁÓˆÛ˘ ÂÍ·ÚÙ¿Ù·È ·fi ÙË ‚·Ú‡ÙËÙ· ÙˆÓ Û˘ÌÙˆÌ¿ÙˆÓ Î·È Î˘Ì·›ÓÂÙ·È ·fi 9 ÌËÓÒÓ Ì¤¯ÚÈ 8 ÂÙÒÓ (61). ªÂÙ·ÏÏ¿ÍÂȘ ÛÙÔ Prop-1 ÁÔÓ›‰ÈÔ Û˘Óԉ‡ÔÓÙ·È ·fi ÛÔ‚·Ú¤˜ Î·È Û˘Ó‰˘·Ṳ̂Ó˜ ·Ó¿ÚÎÂȘ Ù˘ GH, LH, FSH, TSH, Ù˘ ÚÔÏ·ÎÙ›Ó˘ Î·È ›Ûˆ˜ ·ÚÁfiÙÂÚ· Ù˘ ÊÏÔÈÔÙÚfiÔ˘ ÔÚÌfiÓ˘ (ACTH) (62). ŒÙÛÈ, Prop-1 ‰È·Ù·Ú·¯¤˜ Û˘Ó·ÓÙÒÓÙ·È Û¯ÂÙÈο Û˘¯Ó¿ ÛÙȘ ÌÂÈÎÙ¤˜ ·Ó¿ÚÎÂȘ Ù˘ ˘fiÊ˘Û˘ (59). ™Â Û‡ÁÎÚÈÛË Ì ÙÔ˘˜ ·ÛıÂÓ›˜ Ô˘ ¤¯Ô˘Ó ÌÂÙ·ÏÏ¿ÍÂȘ ÛÙÔ POUIF-1 ÁÔÓ›‰ÈÔ, ÔÈ ÔÔ›ÔÈ ¤¯Ô˘Ó Û˘Ó‹ıˆ˜ Ï‹ÚË ¤ÏÏÂÈ„Ë GH Î·È PRL, ÔÈ ·ÛıÂÓ›˜ ÌÂ
ÌÂÙ·ÏÏ¿ÍÂȘ ÛÙÔ Prop-1 ¤¯Ô˘Ó ¯·ÌËÏ¿ ›‰· ·˘ÙÒÓ ÙˆÓ ÔÚÌÔÓÒÓ, ÂÓÒ ¤¯Ô˘Ó Ï‹ÚË ¤ÏÏÂÈ„Ë ÁÔÓ·‰ÔÙÚÔÈÓÒÓ (FSH, LH). ∆Ô ¤Ó· ÙÚ›ÙÔ ÙˆÓ ·ÛıÂÓÒÓ
·ÚÔ˘ÛÈ¿˙ÂÈ Î·È ¤ÏÏÂÈ„Ë Ù˘ ÊÏÔÈÔÙÚfiÔ˘ ÔÚÌfiÓ˘ (ACTH) (8).
™ÙÔ˘˜ ·ÛıÂÓ›˜, ÂÔ̤ӈ˜, Ì ÌÂÙ·ÏÏ¿ÍÂȘ ÛÙÔ Prop-1 ÁÔÓ›‰ÈÔ ‰ÂÓ Â›Ó·È ÂÊÈÎÙ‹ Ë ¤ÎÊÚ·ÛË ÙÔ˘ Pit1 ·fi ÙÔ POUIF-1 ÁÔÓ›‰ÈÔ Î·È, ˆ˜ ÂÎ ÙÔ‡ÙÔ˘, ‰ÂÓ Â›Ó·È ‰˘Ó·Ùfi Ó· ÂÎÎÚ›ÓÔ˘Ó ·˘ÍËÙÈ΋ ÔÚÌfiÓË (GH), ˆ¯ÚÈÓÔÔÈËÙÈ΋ (LH), ı˘Ï·ÎÈÔÙÚfiÔ (FSH), ÚÔÏ·ÎÙ›ÓË (PRL), ı˘ÚÂÔÙÚfiÔ (TSH) Î·È ÊÏÔÈÔÙÚfiÔ ÔÚÌfiÓË (ACTH), Ì ·ÔÙ¤ÏÂÛÌ· Ó· ··ÈÙÂ›Ù·È ıÂڷ›· ˘ÔηٿÛÙ·Û˘ (9).
°ÔÓ›‰ÈÔ L∏Ã3 Î·È ÌÂÙ·ÏÏ¿ÍÂȘ O LHX3 (LIM homeobox3) Â›Ó·È Î·È ·˘Ùfi˜ ¤Ó·˜ ·Ú¿ÁÔÓÙ·˜ ÌÂÙ·ÁÚ·Ê‹˜ Ô˘ ÂÚÈÏ·Ì‚¿ÓÂÈ “ÔÌÔÈÔÂÚÈÔ¯‹” (homeodomain-containing tran-scription factor) Î·È ÂÌÊ·Ó›˙ÂÙ·È Ôχ ÓˆÚ›˜, ηٿ ÙËÓ ÂÔ¯‹ Ù˘ ÔÚÁ·ÓÔÁ¤ÓÂÛ˘ Ù˘ ˘fiÊ˘Û˘ ·fi ÙÔ ı‡Ï·ÎÔ ÙÔ˘ Rathke. O ·Ú¿ÁˆÓ L∏Ã3 ‰Ú· Û˘ÓÂÚÁ·ÙÈο Ì ÙÔ Pit-1 ÛÙË ÌÂÙ·ÁÚ·Ê‹ ÙˆÓ ÂÓÂÚÁÒÓ ÁÔÓȉ›ˆÓ Ô˘ Ú˘ıÌ›˙Ô˘Ó ÙË ‰È·ÊÔÚÔÔ›ËÛË Ù˘ ˘fiÊ˘Û˘ (63). O LHX3 Ú˘ıÌ›˙ÂÈ ÙÔÓ ÔÏÏ·Ï·ÛÈ·ÛÌfi Î·È ÙË ‰È·ÊÔÚÔÔ›ËÛË ÙˆÓ ÛˆÌ·ÙÔÙÚfiˆÓ, Ï·ÎÙÔÙÚfiˆÓ, ı˘ÚÂÔÙÚfiˆÓ Î·È ÁÔÓ·‰ÔÙÚfiˆÓ ΢ÙÙ¿ÚˆÓ Ù˘ ˘fiÊ˘Û˘ (64).
ªÂÙ·ÏÏ¿ÍÂȘ ¤¯Ô˘Ó ÂÚÈÁÚ·Ê› Ôχ ÚfiÛÊ·Ù· ÛÙÔ L∏Ã3 ÁÔÓ›‰ÈÔ Î·È ÚfiÎÂÈÙ·È ÁÈ· ·ÚÂÚÌËÓ‡ÛÈ̘ ÌÂÙ·ÏÏ¿ÍÂȘ (missence) ‹ ·ÒÏÂȘ ‚¿ÛÂˆÓ (deletion), ÔÈ Ôԛ˜ ÎÏËÚÔÓÔÌÔ‡ÓÙ·È Ì ˘ÔÏÂÈfiÌÂÓÔ ¯·Ú·ÎÙ‹Ú·. OÈ ·ÛıÂÓ›˜ ·˘ÙÔ› ·ÚÔ˘ÛÈ¿˙Ô˘Ó ÛÔ‚·Ú‹ ηı˘ÛÙ¤ÚËÛË ÛÙËÓ ·Ó¿Ù˘ÍË Î·È ¤¯Ô˘Ó ÎÔÓÙfi Î·È ¯ÔÓ‰Úfi ·˘¯¤Ó· Ì ÂÚÈÔÚÈṲ̂ÓË ÛÙÚÔÊ‹ Ù˘ ÎÂÊ·Ï‹˜. ∂›Û˘, ÂÌÊ·Ó›˙Ô˘Ó ˘ÔÏ·Û›·Ù˘
˘fiÊ˘Û˘ Î·È ‰‡Ó·Ù·È Ó· ·ÚÔ˘ÛÈ¿˙Ô˘Ó ‰È·Ù·Ú·-
¯¤˜ ÙÔ˘ Ó¢ÚÈÎÔ‡ Û˘ÛÙ‹Ì·ÙÔ˜ (65,66).
∞ÛıÂÓ›˜ Ì ÌÂÙ·ÏÏ¿ÍÂȘ ÛÙÔ LHX3 ÁÔÓ›‰ÈÔ ·-
ÚÔ˘ÛÈ¿˙Ô˘Ó ‰È·Ù·Ú·¯¤˜ Û fiϘ ÙȘ ÔÚÌÔÓÈΤ˜
ÛÂÈÚ¤˜ ÙÔ˘ ÚfiÛıÈÔ˘ ÏÔ‚Ô‡ Ù˘ ˘fiÊ˘Û˘, ÏËÓ Ù˘ ÊÏÔÈÔÙÚfiÔ˘ ÔÚÌfiÓ˘ (ACTH), ÁÈ’ ·˘Ùfi ¯ÚÂÈ¿˙ÔÓÙ·È Ì·ÎÚÔ¯ÚfiÓÈ· ıÂڷ›· ˘ÔηٿÛÙ·Û˘.
Hesx-1 (Rpx) Î·È ÌÂÙ·ÏÏ¿ÍÂȘ
∆Ô ÁÔÓ›‰ÈÔ Hesx-1, Ô˘ ÔÓÔÌ¿˙ÂÙ·È Î·È Rpx (Rathke’ pouch homeobox gene), Â›Ó·È ÙÔ ÚÒÙÔ ·fi Ù· Ù¤ÛÛÂÚ· ÔÌÔÈÔÙÈο ÁÔÓ›‰È· (homeobox genes) Ù˘ ˘fiÊ˘Û˘ Ô˘ ÂÎÊÚ¿˙ÂÙ·È Î·Ù¿ ÙË
‰È¿ÚÎÂÈ· ÙˆÓ ÚÒÙˆÓ ÛÙ·‰›ˆÓ ·Ó¿Ù˘Í˘ Ù˘ ˘fiÊ˘Û˘ Î·È ‚Ú›ÛÎÂÙ·È ÛÙÔÓ ¿ÓıÚˆÔ ÛÙÔ ¯ÚˆÌfiۈ̷ 3 (3p21.2) (67,68).
∏ ·Ô˘Û›· Ù˘ Hesx-1 ÚˆÙ½Ó˘ ÛÙ· ÔÓÙ›ÎÈ· ÈÛÙ‡ÂÙ·È fiÙÈ ÚÔηÏ› ‰È·Ù·Ú·¯¤˜ ÛÙÔ ÎÂÓÙÚÈÎfi Ó¢ÚÈÎfi Û‡ÛÙËÌ· Î·È ‰˘ÛÏ·Û›· Ù˘ ˘fiÊ˘Û˘ (69). ¶Ôχ ÌÈÎÚfi˜ ·ÚÈıÌfi˜ ÌÂÙ·ÏÏ¿ÍÂˆÓ ÛÙÔ Hesx1 ·ÓıÚÒÈÓÔ ÁÔÓ›‰ÈÔ ¤¯ÂÈ ·Ó·ÊÂÚı› ÚfiÛÊ·Ù·, ÔÈ Ôԛ˜ ÎÏËÚÔÓÔÌÔ‡ÓÙ·È Ì ˘ÔÏÂÈfiÌÂÓÔ ‹ Ì ÂÈÎÚ·ÙÔ‡ÓÙ· ¯·Ú·ÎÙ‹Ú·. OÈ ÌÂÙ·ÏÏ¿ÍÂȘ ·˘Ù¤˜ Ê·›ÓÂÙ·È Ó· Â›Ó·È ˘Â‡ı˘Ó˜ ÁÈ· ¤Ó· ÌÈÎÚfi ÔÛÔÛÙfi ·ÛıÂÓÒÓ Ì ˘ÔÊ˘Ûȷ΋ ·Ó¿ÚÎÂÈ·, ÂÓÒ ·Ó¢ڛÛÎÔÓÙ·È Î˘Ú›ˆ˜ Û ·ÛıÂÓ›˜ ÌÂ Û˘ÁÁÂÓ‹ ÔÙÈ΋ ·ÙÚÔÊ›·, fiˆ˜ Ë ‰È·ÊÚ·ÁÌ·ÙÔ-ÔÙÈ΋ ‰˘ÛÏ·Û›· (Û‡Ó‰ÚÔÌÔ Morsier), ηıÒ˜ Î·È Û ·ÛıÂÓ›˜ Ì ˘ÔÏ·Û›· ÙÔ˘ ÚfiÛıÈÔ˘ ÏÔ‚Ô‡ Ù˘ ˘fiÊ˘Û˘ (69,6). ∂ÈÚfiÛıÂÙ·, ÔÈ ·ÛıÂÓ›˜ ·˘ÙÔ› ÌÔÚ› Ó· ·ÚÔ˘ÛÈ¿ÛÔ˘Ó ÌÂÈÎÙ‹ ·Ó¿ÚÎÂÈ· ˘fiÊ˘Û˘ ηÈ, ˆ˜ ÂÎ ÙÔ‡ÙÔ˘, Ó· ¯ÚÂÈ¿˙ÔÓÙ·È ıÂڷ›· ˘ÔηٿÛÙ·Û˘ (69).
™˘¯ÓfiÙËÙ· ÁÂÓÂÙÈÎÒÓ ·ÓˆÌ·ÏÈÒÓ Û ·ÛıÂÓ›˜ Ì ·Ó¿ÚÎÂÈ· ·˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘ (GHD) OÈ ÌÂÙ·ÏÏ¿ÍÂȘ ÛÙ· ÚÔ·Ó·ÊÂÚfiÌÂÓ· ÁÔÓ›‰È· ·Ó¢ڛÛÎÔÓÙ·È Û¯ÂÙÈο Û¿ÓÈ·. ∞˘Ùfi Û˘Ì‚·›ÓÂÈ ‰ÈfiÙÈ ÙȘ ÂÚÈÛÛfiÙÂÚ˜ ÊÔÚ¤˜ Ë ÁÂÓÂÙÈ΋ ·Ó¿Ï˘ÛË ÂÊ·ÚÌfi˙ÂÙ·È Û ηıÔÚÈṲ̂ÓÔ˘˜ ·ÛıÂÓ›˜ Î·È ÌÂ Û˘ÁÎÂÎÚÈ̤ÓË Î·Ù‡ı˘ÓÛË ¤Ú¢ӷ˜. °È· ÙÔ ÏfiÁÔ ·˘Ùfi, ÚÔ˜ ÙÔ ·ÚfiÓ, Ë ÁÂÓÂÙÈ΋ ·Ó¿Ï˘ÛË DNA ·Ï¿ ÂȂ‚·ÈÒÓÂÈ ÙË ‰È¿ÁÓˆÛË Ù˘ ·Ó¿ÚÎÂÈ·˜ GH, Ë ÔÔ›· Á›ÓÂÙ·È ˆ˜ ÁÓˆÛÙfi ·fi ÙËÓ ÎÏÈÓÈ΋ ÂÈÎfiÓ· Î·È ÙȘ ÁÓˆÛÙ¤˜ ‰ÔÎÈ̷ۛ˜ ÚfiÎÏËÛ˘. ∂Í¿ÏÏÔ˘, Ë ·Ó·Ï˘ÙÈ΋ ÂͤٷÛË DNA Â›Ó·È Ì›· ¯ÚÔÓÔ‚fiÚ· Î·È ·ÎÚÈ‚‹ ̤ıÔ‰Ô˜, Ì ·ÔÙ¤ÏÂÛÌ· Ó· ÌËÓ ÌÔÚ›, ÚÔ˜ ÙÔ ·ÚfiÓ, Ó· Á›ÓÂÈ Ì¤ıÔ‰Ô˜ ÚÔ˘Ù›Ó·˜. ™˘¯ÓfiÙËÙ· ÁÂÓÂÙÈÎÒÓ ‰È·Ù·Ú·¯ÒÓ
Ì ÌÂÌÔӈ̤ÓË ·Ó¿ÚÎÂÈ· ˘fiÊ˘Û˘ (IGHD) (6,17,70). ∞ÓÙ›ÛÙÔȯ·, Ë Û˘¯ÓfiÙËÙ· ÌÂÙ·ÏÏ¿ÍÂˆÓ ÛÙÔ GHRHR ÁÔÓ›‰ÈÔ Ê·›ÓÂÙ·È Ó· Â›Ó·È Ôχ ÌÈÎÚfiÙÂÚË. ø˜ ÂÎ ÙÔ‡ÙÔ˘, Ë ÏÂÈÔ„ËÊ›· ÙˆÓ ÂÚÈÙÒÛÂˆÓ Ì ÌÂÌÔӈ̤ÓË ·Ó¿ÚÎÂÈ· ·˘ÍËÙÈ΋˜
ÔÚÌfiÓ˘ (IGHD) ÂÍ·ÎÔÏÔ˘ı› Ó· ¯·Ú·ÎÙËÚ›˙ÂÙ·È
ˆ˜ ȉÈÔ·ı‹˜.
∆· ÂÚÈÔÚÈṲ̂ӷ Û˘ÌÂÚ¿ÛÌ·Ù· ÙˆÓ ‰È·ÊfiÚˆÓ
ÌÂÏÂÙÒÓ Û‡Ìʈӷ Ì ÙÔ˘˜ ›‰ÈÔ˘˜ ÂÚ¢ÓËÙ¤˜, ÔÊ›ÏÔÓÙ·È ÛÙÔ ÁÂÁÔÓfi˜ fiÙÈ ·˘Ù¤˜ ÛÙÚ¤ÊÔÓÙ·È Î˘Ú›ˆ˜
ÛÙËÓ ˘fiÊ˘ÛË, ÂÓÒ ıˆÚÂ›Ù·È fiÙÈ Ù· 2/3 ÂÚ›Ô˘
ÙˆÓ ·ÛıÂÓÒÓ Ì IGHD ¤¯Ô˘Ó ˘Ôı·Ï·ÌÈ΋ Ì¿ÏÏÔÓ,
·Ú¿ ˘ÔÊ˘Ûȷ΋ ·ÓˆÌ·Ï›· (6). ™‹ÌÂÚ·, ÈÛÙ‡ÂÙ·È fiÙÈ ÛÙË ÏÂÙ‹ ÂÈÎÔÈÓˆÓ›· ˘Ôı·Ï¿ÌÔ˘-˘fiÊ˘-
Û˘ ÂÌϤÎÔÓÙ·È ·Ú¿ÁÔÓÙ˜ ÏÈÁfiÙÂÚÔ ‰È¢ÎÚÈÓÈṲ̂ÓÔÈ ·fi ÂΛÓÔ˘˜ Ô˘ ÂÓ¤¯ÔÓÙ·È ÛÙË ‰È·ÊÔÚÔÔ›ËÛË Ù˘ ˘fiÊ˘Û˘ (6).
ÙÂÏÂ˘Ù·›· ¯ÚfiÓÈ·, Ë Ù·˘ÙÔÔ›ËÛË ÙˆÓ ·Ú·ÁfiÓÙˆÓ ÌÂÙ·ÁÚ·Ê‹˜ (Transcription factors), ÔÈ ÔÔ›ÔÈ ÂÌϤÎÔÓÙ·È ÛÙËÓ ·Ó¿Ù˘ÍË Î·È ÙË ‰È·ÊÔÚÔ-
Ù˘ ˘fiÊ˘Û˘, Ì¿˜ ‚ÔËı¿ Ó· ηٷÓÔ‹ÛÔ˘-
·ıÔÁ¤ÓÂÛË ÙˆÓ ‰È·ÊÔÚÂÙÈÎÒÓ Ù‡ˆÓ ÔÏ-
·Ó¿ÚÎÂÈ·˜ ˘fiÊ˘Û˘ (CPHD). ™‡Ìʈӷ Ì ÙÔ˘˜ Pfaffle Î·È Û˘Ó, ÔÈ ÌÈÛÔ› ·fi ÙÔ˘˜ ·ÛıÂÓ›˜
Ì ·Ó¿ÚÎÂÈ· GH, TSH Î·È ÚÔÏ·ÎÙ›Ó˘ ¤¯Ô˘Ó
‰È·ÎÚÈÙ¤˜ ÌÂÙ·ÏÏ¿ÍÂȘ ÛÙÔ POUIF-1 ÁÔÓ›‰ÈÔ, ÂÓÒ Ù· 2/3 ÙˆÓ ·ÛıÂÓÒÓ Ì ·Ó¿ÚÎÂÈ· GH, TSH, PRL Î·È ÁÔÓ·‰ÔÙÚÔÈÓÒÓ ¤¯Ô˘Ó ÌÂÙ·ÏÏ¿ÍÂȘ ÛÙÔ Prop-1 ÁÔÓ›‰ÈÔ.
OÈ ÌÂÙ·ÏÏ¿ÍÂȘ ÛÙÔ Hesx-1 ÁÔÓ›‰ÈÔ, Ô˘ ÂÎÊÚ¿˙ÔÓÙ·È ÓˆÚ›˜ ηٿ ÙË ‰È¿ÚÎÂÈ· Ù˘ ÂÌÊ¿ÓÈÛ˘ ηÈ
‰È·ÊÔÚÔÔ›ËÛ˘ Ù˘ ˘fiÊ˘Û˘, Â›Ó·È Ôχ ÂÚÈÔÚÈṲ̂Ó˜ Î·È ˘ÔÏÔÁ›˙ÔÓÙ·È Û ÏÈÁfiÙÂÚÔ ·fi 1%
ÙˆÓ ·ÛıÂÓÒÓ Ì CPHD. ∆¤ÏÔ˜, Â›Ó·È ‰‡ÛÎÔÏÔ, ÚÔ˜ ÙÔ ·ÚfiÓ, Ó· ˘ÔÏÔÁÈÛÙ› Ë Û˘¯ÓfiÙËÙ· ÙˆÓ LHX3 ÌÂÙ·ÏÏ¿ÍÂˆÓ ÛÙÔÓ ¿ÓıÚˆÔ, ÏfiÁˆ ÙÔ˘ ÂÚÈÔÚÈṲ̂ÓÔ˘ ·ÚÈıÌÔ‡ ÂÚÈÙÒÛˆÓ.
™˘ÌÂÚ¿ÛÌ·Ù·
∏ ÁÂÓÂÙÈ΋ ·Ó¿Ï˘ÛË ÛÙÔ˘˜ ·ÛıÂÓ›˜ Ì ˘ÔÊ˘Ûȷ΋ ·Ó¿ÚÎÂÈ· ÌÔÚ› Ó· ·Ú¿Û¯ÂÈ ÙË ‰˘Ó·ÙfiÙËÙ· ÁÈ· ¤ÁηÈÚË Î·È ÂȉÈ΋ ·ÓÙÈÌÂÙÒÈÛË, ‰ÈfiÙÈ ı·
Á›ÓÂÙ·È ·ÓÙÈÏËÙ‹ Ë ÛÔ‚·ÚfiÙËÙ· ÙÔ˘ ÚÔ‚Ï‹Ì·ÙÔ˜, ηıÒ˜ Î·È ÔÈ ‚Ú·¯˘ÚfiıÂÛ̘ Î·È Ì·ÎÚÔÚfiıÂÛ̘ Û˘Ó¤ÂȤ˜ ÙÔ˘. ∂›Û˘, Ë ·Ó·Î¿Ï˘„Ë ÙÔ˘ ›‰Ô˘˜ ÙˆÓ ÌÂÙ·ÏÏ¿ÍÂˆÓ ÙˆÓ ÁÔÓȉ›ˆÓ Ô˘ ÂÓ¤¯ÔÓÙ·È ÛÙÔÓ Û¯ËÌ·ÙÈÛÌfi Î·È ÙË ÏÂÈÙÔ˘ÚÁ›· ÙÔ˘ ÚfiÛıÈÔ˘ ÏÔ‚Ô‡ Ù˘ ˘fiÊ˘Û˘, ÌÔÚ› Ó· ‰ÒÛÂÈ ÔχÙÈ̘ ÏËÚÔÊÔڛ˜ Û¯ÂÙÈο Ì ÙÔÓ ÙÚfiÔ ÎÏËÚÔÓÔÌÈÎfiÙËÙ·˜ ÙˆÓ ‰È·ÊfiÚˆÓ ‰È·Ù·Ú·¯ÒÓ
µÈ‚ÏÈÔÁÚ·Ê›·
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HÌÂÚÔÌËÓ›· ˘Ô‚ÔÏ‹˜: 29-07-2002
HÌÂÚÔÌËÓ›· ¤ÁÎÚÈÛ˘: 31-01-2003
¢È‡ı˘ÓÛË ·ÏÏËÏÔÁÚ·Ê›·˜: ª·Ú›·-™Ù¤ÏÏ· §·Ú›Ô˘
π¤ÚˆÓÔ˜ 13, ∆.∫. 116 34, ¶·ÁÎÚ¿ÙÈ, ∞ı‹Ó·
∞ÌÊÔÙÂÚfiÏ¢ÚÔÈ ÏÂÈÔ΢ÛÙÈÎÔ› ÓÂÊÚÔ›
∏ ÏÂÈÔ΢ÛÙÈ΋ ‰˘ÛÏ·Û›· ÙˆÓ ÓÂÊÚÒÓ Â›Ó·È Û¯ÂÙÈο Û˘-
¯Ó‹ ·ÈÙ›· ÓÂÊÚÈ΋˜ Ì¿˙·˜ ÛÙ· ÓÂÔÁÓ¿, ¤¯ÂÈ Î·Ï‹ ÚfiÁÓˆÛË Î·È
Û˘Ó‹ıˆ˜ ‰È·ÈÛÙÒÓÂÙ·È ÛÙÔÓ ¤Ó· ÓÂÊÚfi. ∂›Ó·È ·ÁÓÒÛÙÔ˘ ·È-
ÙÈÔÏÔÁ›·˜ Î·È Û ÔÚÈṲ̂ÓÔ˘˜ ·ÛıÂÓ›˜ ÎÏËÚÔÓÔÌÂ›Ù·È Ì ÙÔÓ
ÂÈÎÚ·ÙÔ‡ÓÙ· ۈ̷ÙÈÎfi ¯·Ú·ÎÙ‹Ú·. ™Â ÔÛÔÛÙfi 10-25%, Ô ˘ÁÈ‹˜ ÓÂÊÚfi˜ ·ÚÔ˘ÛÈ¿˙ÂÈ Î˘ÛÙÂÔÔ˘ÚËÙËÚÈ΋ ·ÏÈÓ‰ÚfiÌËÛË
ηÈ, ÈÔ Û¿ÓÈ·, ˘ÂÏÔ-Ô˘ÚËÙËÚÈ΋ ÛÙ¤ÓˆÛË, ‰ÈÏ·ÛÈ·ÛÌfi ÙÔ˘
˘ÂÏÔÎ·Ï˘ÎÈÎÔ‡ Û˘ÛÙ‹Ì·ÙÔ˜, ¤ÎÙÔÔ Ô˘ÚËÙ‹Ú· ‹ Ô˘ÚËÙËÚÔ΋ÏË.
∏ ÂÌÊ¿ÓÈÛË ·ÌÊÔÙÂÚfiÏ¢Ú˘ ÏÂÈÔ΢ÛÙÈ΋˜ ‰˘ÛÏ·Û›·˜ Â›Ó·È Û˘Ó‹ıˆ˜ ı·Ó·ÙËÊfiÚÔ˜ ÛÙËÓ ÂÌ‚Ú˘˚΋ ˙ˆ‹ Î·È ‰È·ÈÛÙÒÓÂÙ·È ÛÙÔ 7-23% ÙˆÓ ·ÛıÂÓÒÓ. ™ÙËÓ ÂÚ›ÙˆÛË Ô˘ Â-
ÚÈÁÚ¿ÊÂÙ·È, Ë ·ÛıÂÓ‹˜ Ì ·ÌÊÔÙÂÚfiÏ¢ÚÔ˘˜ ÏÂÈÔ΢ÛÙÈ-
ÎÔ‡˜ ÓÂÊÚÔ‡˜ ·ÚÔ˘Û›·˙ ΢ÛÙÈ΋ ‰˘ÛÏ·Û›· ÌfiÓÔ ÛÙÔ ¿Óˆ
ÙÌ‹Ì· ÙÔ˘ ‰ÂÍÈÔ‡ ÓÂÊÚÔ‡
ÙËÓ ÎÏËÚÔÓÔÌÈ΋ ÌÔÚÊ‹ Ù˘ ÓfiÛÔ˘, ÁÈ·Ù› Î·È ÔÈ ‰‡Ô ÁÔÓ›˜ ·ÚÔ˘Û›·˙·Ó Ê˘ÛÈÔÏÔÁÈÎfi ˘ÂÚ˯ÔÁÚ¿ÊËÌ· ÓÂÊÚÒÓ. ™ÙËÓ ·Ú·ÎÔÏÔ‡ıËÛË, Ë ·ÛıÂÓ‹˜ ‰È·ÙËÚÔ‡ÛÂ Ê˘ÛÈÔÏÔÁÈ΋ ÓÂÊÚÈ΋ ÏÂÈÙÔ˘ÚÁ›·, fï˜ Ë ÚfiÁÓˆÛË Â›Ó·È ÂÈÊ˘Ï·ÎÙÈ΋ ÏfiÁˆ Ù˘ ÛËÌ·ÓÙÈ΋˜ ÂÏ¿ÙÙˆÛ˘ Ù˘ ÏÂÈÙÔ˘ÚÁÈ΋˜ ÓÂÊÚÈ΋˜ Ì¿˙·˜ Ù˘ ·ÛıÂÓÔ‡˜ Î·È ÙȘ ‚Ï¿‚˜ Ô˘ Èı·ÓÒ˜ ı· ÚÔ·„Ô˘Ó ÛÙÔ Ì¤ÏÏÔÓ ·fi ÙËÓ ·˘ÍË̤ÓË ÛÂÈÚ·Ì·ÙÈ΋ ˘ÂډȋıËÛË.
1Agrawal L, Millard ML, Fairhurst J, Gilbert RD Bilateral multicystic kidneys - an unusual case Pediatr Nephrol 2002;17:964-965
™ÙÂÊ·Ó›‰Ë˜ ∫. π. ∞Ó·ÏËÚˆÙ‹˜ ¢È¢ı˘ÓÙ‹˜ ¡ÂÊÚÔÏÔÁÈÎÔ‡ ∆Ì‹Ì·ÙÔ˜
¡ÔÛÔÎÔÌÂ›Ô ¶·›‰ˆÓ “¶. & ∞. ∫˘ÚÈ·ÎÔ‡”
™‡Ó‰ÚÔÌ· ÙÔÍÈ΋˜ ηٷÏËÍ›·˜ ÛÙ· ·È‰È¿
°. ™È‰¤ÚË, ∞. µ·ÛÈÏfiÔ˘ÏÔ˜
Toxic shock syndromes
G. Sideri, A. Vassilopoulos
¶ÂÚ›ÏË„Ë: ∆Ô Û‡Ó‰ÚÔÌÔ ÙÔÍÈ΋˜ ηٷÏËÍ›·˜ (TSS) ·ÔÙÂÏ› Ì›· Û¿ÓÈ·, ·ÏÏ¿ Ôχ ‚·ÚÈ¿ ÎÏÈÓÈ΋ ÔÓÙfiÙËÙ· ÛÙ· ·È‰È¿. OÈ ·ıÔÏÔÁÈΤ˜ ηٷÛÙ¿ÛÂȘ Ô˘ ÙÔ ÚÔηÏÔ‡Ó Â›Ó·È ÔÍ›˜ ÔÏ˘Û˘ÛÙËÌ·ÙÈΤ˜ ‰È·Ù·Ú·¯¤˜, Ô˘ Û˘Óԉ‡ÔÓÙ·È ·fi Ïԛ̈ÍË
‹ ·ÔÈÎÈÛÌfi Ì ÛÙÂϤ¯Ë Staphylococcus aureus ‹ Streptococcus pyogenes, Ù· ÔÔ›· ·Ú¿ÁÔ˘Ó Â͈ÙÔ͛Ә ÈηӤ˜ Ó· ‰Ú¿ÛÔ˘Ó Û·Ó ˘ÂÚ·ÓÙÈÁfiÓ·. ¶·Ú¿ ÙÔÓ ÎÏÈÓÈÎfi ‰È·¯ˆÚÈÛÌfi ÙÔ˘ ÛÙ·Ê˘ÏÔÎÔÎÎÈÎÔ‡ TSS ·fi ÙÔ ÛÙÚÂÙÔÎÔÎÎÈÎfi TSS, Ô ·ıÔÁÂÓÂÙÈÎfi˜ Ì˯·ÓÈÛÌfi˜ ıˆÚÂ›Ù·È fiÙÈ Â›Ó·È Ô ›‰ÈÔ˜. ∏ ˘ÂÚ·ÓÙÈÁÔÓÈ΋ ‰Ú·ÛÙËÚÈfiÙËÙ· ¤¯ÂÈ ˆ˜ ·ÔÙ¤ÏÂÛÌ· ÙËÓ ·ÂÏ¢ı¤ÚˆÛË ÚÔÊÏÂÁÌÔÓˆ‰ÒÓ Î˘ÙÙ·ÚÔÎÈÓÒÓ, Ë ‰Ú¿ÛË ÙˆÓ ÔÔ›ˆÓ ÚÔηÏ› ÙȘ Û˘ÛÙËÌ·ÙÈΤ˜ ·ıÔÊ˘ÛÈÔÏÔÁÈΤ˜ ‰È·Ù·Ú·¯¤˜ ÙÔ˘ Û˘Ó‰ÚfiÌÔ˘ (˘fiÙ·ÛË, ÔÏ˘ÔÚÁ·ÓÈ΋ ·Ó¿ÚÎÂÈ·). ∆Ô Û‡Ó‰ÚÔÌÔ ¯·Ú·ÎÙËÚ›˙ÂÙ·È ÎÏÈÓÈο ·fi ˘ÚÂÙfi, ‰È¿¯˘ÙÔ ÎËÏȉ҉˜ ÂÍ¿ÓıËÌ·, ˘fiÙ·ÛË Î·È ÔÏ˘ÔÚÁ·ÓÈ΋ ·Ó¿ÚÎÂÈ·. °È· ÙËÓ ÂÈÙ˘¯‹ ·ÓÙÈÌÂÙÒÈÛË ÙÔ˘ Û˘Ó‰ÚfiÌÔ˘ ÛËÌ·ÓÙÈÎfi ÚfiÏÔ ·›˙ÂÈ Ë ·ÓÙÈÌÈÎÚԂȷ΋ ·ÁˆÁ‹, ·ÏÏ¿ ΢ڛˆ˜ Ë ¤ÁηÈÚË ·ÓÙÈÌÂÙÒÈÛË Ù˘ ΢ÎÏÔÊÔÚÈ΋˜ ηٷÏËÍ›·˜, Ë ‰È·Ù‹ÚËÛË ÈηÓÔÔÈËÙÈ΋˜ ηډȷ΋˜ ·ÚÔ¯‹˜ (¯ÔÚ‹ÁËÛË ˘ÁÚÒÓ, ÈÓÔÙÚfiˆÓ) Î·È Ë ·ÔηٿÛÙ·ÛË ÙˆÓ ‰È·Ù·Ú·¯ÒÓ ÔÌÔÈfiÛÙ·Û˘.
§¤ÍÂȘ ÎÏÂȉȿ: Û‡Ó‰ÚÔÌ· ÙÔÍÈ΋˜ ηٷÏËÍ›·˜, ÛÙÚÂÙÔÎÔÎÎÈÎfi ÙÔÍÈÎfi Û‡Ó‰ÚÔÌÔ, ÛÙ·Ê˘ÏÔÎÔÎÎÈÎfi ÙÔÍÈÎfi Û‡Ó‰ÚÔÌÔ, ÙÔÍ›ÓË ÙÔ˘ Û˘Ó‰ÚfiÌÔ˘ Ù˘ ÙÔÍÈ΋˜ ηٷÏËÍ›·˜.
Abstract: The toxic shock syndrome (TSS) is an uncommon but severe clinical problem in children. The pathological conditions that precipitate this syndrome are acute multisystem disorders, associated with infection/colonization by strains of Staphylococcus aureus or Streptococcus pyogenes (and rarely other streptococcal species) which produce exotoxins capable of acting as superantigens. Although clinically distinct, staphylococcal and streptococcal types of TSS are believed to share this common pathogenetic mechanism. Superantigen activity results in a massive release of proinflammatory cytokines which cause multisystem disorders. Clinically the syndrome is characterized by fever, hypotension, erythroderma, and multisystem failure. The successful management of TSS is based on the administration of appropriate antibiotic agents, but primarily on the timely management of circulatory shock (fluid balance, use of inotropic agents) and the conservation of adequate cardiac output).
Key words: toxic shock syndrome, streptococcal toxic shock syndrome, staphylococcal toxic shock syndrome, toxic shock syndrome toxin-1. ™˘ÓÙÔÌÔÁڷʛ˜
TSSToxic shock syndrome
TSST-1Toxic shock syndrome toxin-1
TNFTumor necrosis factor IL-1Interleukin 1
ªÔÓ¿‰· ∂ÓÙ·ÙÈ΋˜ £Âڷ›·˜ ¶·È‰ÈÒÓ, ¡ÔÛÔÎÔÌÂ›Ô ¶·›‰ˆÓ “¶. & ∞. ∫˘ÚÈ·ÎÔ‡”, ∞ı‹Ó·
TCRT-cell receptor
Paediatric Intensive Care Unit, “P. & A. Kyriakou”Children’s Hospital, Athens
¶›Ó·Î·˜ 1. ¢ÂÚÌ·ÙÈΤ˜ ÂΉËÏÒÛÂȘ ÙÔ˘ TSS
∂Ή‹ÏˆÛËÃÚfiÓÔ˜ ÂÌÊ¿ÓÈÛ˘
ñ °ÂÓÈÎÂ˘Ì¤ÓË ÎËÏȉ҉˘ ÂÚ˘ıÚÔ‰ÂÚÌ›·¶ÚÒÈÌË (Û˘¯Ó¿ ·ÚÔ‰È΋)
ñ ∂ί˘ÌÒÛÂȘ (·Û˘Ó‹ı˘)¶ÚÒÈÌË
ñ ∂Ú˘ıÚfiÙ˘ ·Ï·ÌÒÓ-ÂÏÌ¿ÙˆÓ¶ÚÒÈÌË
ñ °ÂÓÈÎÂ˘Ì¤ÓÔ Ô›‰ËÌ·¶ÚÒÈÌË
ñ ºÏ‡ÎÙ·ÈÓ˜-Ê˘Û·Ï›‰Â˜ (·Û˘Ó‹ı˘)¶ÚÒÈÌË
ñ ∫ÓȉˆÙÈÎfi ÎËÏȉԂϷÙȉ҉˜ ÂÍ¿ÓıËÌ·7-14 Ë̤Ú˜
ñ ∞ÔϤÈÛË ‰·ÎهψÓ-·Ï·ÌÒÓ-ÂÏÌ¿ÙˆÓ10-21 Ë̤Ú˜
ñ ∞ÒÏÂÈ· Ì·ÏÏÈÒÓ-ÔÓ‡¯ˆÓ4-12 ‚‰ÔÌ¿‰Â˜
ñ ŒÓÙÔÓÔ ÂÚ‡ıËÌ· ÂÈÂÊ˘ÎfiÙˆÓ Î·È ‚ÏÂÓÓÔÁfiÓˆÓ (ÛÙfiÌ·ÙÔ˜, ÁÏÒÛÛ·˜, Ê¿Ú˘ÁÁ·-ÎfiÏÔ˘, Ù˘Ì·ÓÈ΋˜ ÌÂÌ‚Ú¿Ó˘)
ñ ªÔÚÔÂȉ‹˜ ÁÏÒÛÛ·
ñ ∞ÈÌÔÚÚ·Á›Â˜ ˘fi ÙÔÓ ÂÈÂÊ˘ÎfiÙ·
ñ ∂ÍÂÏÎÒÛÂȘ ÛÙfiÌ·ÙÔ˜-ÎfiÏÔ˘-ÔÈÛÔÊ¿ÁÔ˘-·ÛÙˆ˜
Staphylococcus aureus ÌÔÚ› Ó· ·ÔÌÔÓˆı›
·fi ÙËÓ ÂÛÙ›· Ïԛ̈͢ Û ÔÛÔÛÙfi >85% ÙˆÓ Â-
ÚÈÙÒÛˆÓ.
∆· ·ÓÙÈÛÒÌ·Ù· ¤Ó·ÓÙÈ Ù˘ TSST-1 ηٿ ÙËÓ
ÔÍ›· Ê¿ÛË ·Ô˘ÛÈ¿˙Ô˘Ó, ÂÓÒ Î·Ù¿ ÙËÓ ·Ó¿ÚÚˆÛË
˘¿Ú¯ÂÈ ˘„ËÏfi˜ Ù›ÙÏÔ˜ ·ÓÙÈۈ̿وÓ. OÈ ·ÈÌÔηÏ-
ÏȤÚÁÂȘ ·Ú·Ì¤ÓÔ˘Ó ÛÙ›Ú˜ ηٿ ÙËÓ ÔÍ›· Ê¿ÛË (7).
¢È·ÁÓˆÛÙÈο ÎÚÈÙ‹ÚÈ· ÙÔ˘ staph-TSS ∏ ‰È¿ÁÓˆÛË ÙÔ˘ Û˘Ó‰ÚfiÌÔ˘ ‰ÂÓ ÂÍ·ÚÙ¿Ù·È Ô‡-
Ù ÂȂ‚·ÈÒÓÂÙ·È ·fi ÙËÓ ·ÔÌfiÓˆÛË ÌÈÎÚÔ‚›Ô˘, ÙËÓ ·Ó›¯Ó¢ÛË Â͈ÙÔÍÈÓÒÓ ‹ ·ÓÙÈÛˆÌ¿ÙˆÓ ¤Ó·ÓÙÈ
Â͈ÙÔÍÈÓÒÓ, ·ÏÏ¿ Ù›ıÂÙ·È ·ÔÎÏÂÈÛÙÈο Ì ÎÏÈÓÈο
ÎÚÈÙ‹ÚÈ· (8). ∞˘Ù¿ ÂÚÈÏ·Ì‚¿ÓÔ˘Ó: ·)˘ÚÂÙfi >38,9ÔC, ‚)ÂÍ¿ÓıËÌ· ‰È¿¯˘ÙÔ ÎËÏȉ҉˜, Á)·ÔϤÈÛË ·Ï·ÌÒÓ-ÂÏÌ¿ÙˆÓ 1-2 ‚‰ÔÌ¿-
‰Â˜ ÌÂÙ¿ ÙËÓ ÂΉ‹ÏˆÛË Ù˘ ÓfiÛÔ˘, ‰)˘fiÙ·ÛË (ηıÔÚÈ˙fiÌÂÓË Û·Ó Û˘ÛÙÔÏÈ΋ <90
mmHg ÁÈ· ÙÔ˘˜ ÂÓ‹ÏÈΘ Î·È <5Ë ∂.£. ÁÈ· Ù· ·È‰È¿
ËÏÈΛ·˜ <16 ÂÙÒÓ, ÙÒÛË Ù˘ ‰È·ÛÙÔÏÈ΋˜ ·ÚÙËÚȷ΋˜ ›ÂÛ˘ >15 mmHg ηٿ ÙË ÌÂÙ¿‚·ÛË ·fi ÙËÓ
ηٷÎÂÎÏÈ̤ÓË ÛÙËÓ fiÚıÈ· ı¤ÛË, ÔÚıÔÛÙ·ÙÈÎfi Û˘ÁÎÔ-
ÈÎfi ÂÂÈÛfi‰ÈÔ ‹ ˙¿ÏË ÛÙËÓ fiÚıÈ· ı¤ÛË), Â)ÚÔÛ‚ÔÏ‹ ÙÚÈÒÓ ‹ ÂÚÈÛÛfiÙÂÚˆÓ ·fi Ù· ·ÎfiÏÔ˘ı· ÔÚÁ·ÓÈο Û˘ÛÙ‹Ì·Ù·: Á·ÛÙÚÂÓÙÂÚÈÎÔ‡ (¤ÌÂÙÔÈ ‹ ‰È·ÚÚÔ˚Τ˜ ÎÂÓÒÛÂȘ ÛÙËÓ ¤Ó·ÚÍË Ù˘ ÓfiÛÔ˘), Ì˘˚ÎÔ‡ (ÛËÌ·ÓÙÈ΋ Ì˘·ÏÁ›· ‹ CPK ÔÚÔ‡ >2Ï¿ÛÈÔ Ù˘ Ê˘ÛÈÔÏÔÁÈ΋˜ ÙÈÌ‹˜), ‚ÏÂÓÓÔÁfiÓˆÓ (˘ÂÚ·ÈÌ›· ÂÈÂÊ˘ÎfiÙˆÓ, ÛÙÔÌ·ÙÔÊ¿Ú˘ÁÁ·, ÎfiÏÔ˘), Ô˘ÚÔÔÈËÙÈÎÔ‡ (Ô˘Ú›· ‹ ÎÚ·ÙÈÓ›ÓË ÔÚÔ‡ >2Ï¿ÛÈÔ Ù˘ Ê˘ÛÈÔÏÔÁÈ΋˜ ÙÈÌ‹˜ ‹ ˘ÔÛÊ·›ÚÈ· >5 ÎÔ Â› ·Ô˘Û›·˜ Ô˘ÚÔÏԛ̈͢), ‹·ÙÔ˜ (ÔÏÈ΋ ¯ÔÏÂÚ˘ıÚ›ÓË, SGOT ‹ SGPT >2Ï¿ÛÈÔ Ù˘ Ê˘ÛÈÔÏÔÁÈ΋˜ ÙÈÌ‹˜), ·ÈÌÔÔÈËÙÈÎÔ‡ (·ÈÌÔÂÙ¿ÏÈ· <100.000/mm3) Î·È ∫¡™ (‰È·Ù·Ú·¯¤˜ ÚÔÛ·Ó·ÙÔÏÈÛÌÔ‡ ‹ ÙÔ˘ ÂȤ‰Ô˘ Û˘Ó›‰ËÛ˘, ¯ˆÚ›˜ ÂÛÙȷο Ó¢ÚÔÏÔÁÈο ÛËÌ›·, › ·Ô˘Û›·˜ ˘ÚÂÙÔ‡ Î·È ˘fiÙ·Û˘). ÛÙ)·ÚÓËÙÈο ·ÔÙÂϤÛÌ·Ù· ÙˆÓ ·ÎfiÏÔ˘ıˆÓ ÂÚ-
100
Á·ÛÙËÚÈ·ÎÒÓ ÂÍÂÙ¿ÛˆÓ, Â¿Ó ÏËÊıÔ‡Ó: i) ηÏÏȤÚÁÂȘ ·›Ì·ÙÔ˜ - Ê¿Ú˘ÁÁ· - ∂¡À (Ë Î·ÏÏȤÚÁÂÈ· ·›Ì·ÙÔ˜ ÌÔÚ› Ó· Â›Ó·È ıÂÙÈ΋ ÁÈ· ¯Ú˘Û›˙ÔÓÙ· ÛÙ·Ê˘ÏfiÎÔÎÎÔ) Î·È ii) ÔÚÔÏÔÁÈÎfi˜ ¤ÏÂÁ¯Ô˜ ÁÈ· ÎËÏÈ‰Ò‰Ë ˘ÚÂÙfi ÙˆÓ ‚Ú·¯ˆ‰ÒÓ ÔÚ¤ˆÓ, ÏÂÙÔÛ›ڈÛË
‰È·ÁÓˆÛÙÈο ÎÚÈÙ‹ÚÈ·, Û˘ÌÂÚÈÏ·Ì‚·ÓÔ̤Ó˘ Ù˘ ·ÔϤÈÛ˘ (ÂÎÙfi˜ Â¿Ó Ô ·ÛıÂÓ‹˜ ηٷϋÍÂÈ ÚÈÓ ÙËÓ ÂÌÊ¿ÓÈÛË Ù˘ ·ÔϤÈÛ˘).
£Âڷ›· ∏ ıÂڷ›· ÙÔ˘ staph-TSS ‚·Û›˙ÂÙ·È Û ÙÚÂȘ ‚·ÛÈΤ˜ ·Ú¯¤˜: ·) ÛÙË Ì˯·ÓÈ΋ ·Ê·›ÚÂÛË Ù˘ ÙÔ͛Ӣ Ô˘ ·Ú¿ÁÂÈ o S. aureus, Ì ·ÚÔ¯¤Ù¢ÛË Î·È Ù·˘ÙÔÔ›ËÛË ·fi ÙË ı¤ÛË Ù˘ ·Ú·ÁˆÁ‹˜ Ù˘ ÙÔ͛Ӣ (.¯. Û staph-TSS ·fi ¤ÌÌËÓÔ Ú‡ÛË, ·Ê·›ÚÂÛË ÙÔ˘ tampon). OÈ ÏÔÈÌÒÍÂȘ ÙˆÓ Ì·Ï·ÎÒÓ ÌÔÚ›ˆÓ Î·È ÔÈ ¯ÂÈÚÔ˘ÚÁÈΤ˜ ÏÔÈÌÒÍÂȘ ı· Ú¤ÂÈ Ó· ·ÚÔ¯ÂÙ‡ÔÓÙ·È Î·È Ó· ·Ê·ÈÚÂ›Ù·È ÙÔ Í¤ÓÔ ˘ÏÈÎfi. ‚) ÛÙËÓ ·ÓÙÈÌÈÎÚԂȷ΋ ıÂڷ›·, ÁÈ· Ó· ÛÙ·Ì·Ù‹ÛÂÈ Ë ·Ú·ÁˆÁ‹ Ù˘ ÙÔ͛Ӣ Î·È Ó· ÂÍÔ˘‰ÂÙÂÚˆı› Ô ÌÈÎÚÔÔÚÁ·ÓÈÛÌfi˜. À„ËϤ˜ ‰fiÛÂȘ IV ·ÓÙÈÛÙ·Ê˘ÏÔÎÔÎÎÈ΋˜ ‚-Ï·ÎÙ¿Ì˘ (ÔÍ·ÎÈÏÏ›ÓË, ÊÏÔ˘ÎÏÔÍ·ÎÈÏÏ›ÓË, ÎÂÊ·˙ÔÏ›ÓË) ‹ ‚·ÓÎÔÌ˘Î›Ó˘ Ú¤ÂÈ Ó· ¯ÔÚËÁËıÔ‡Ó ÙÔ Û˘ÓÙÔÌfiÙÂÚÔ ‰˘Ó·Ùfi. ¶Ú¤ÂÈ Ó· ¯ÔÚËÁÔ‡ÓÙ·È ˘„ËϤ˜ ‰fiÛÂȘ Ê·Ú̿ΈÓ, ‰ÈfiÙÈ ÔÈ ¯·ÌËϤ˜ Û˘ÁÎÂÓÙÚÒÛÂȘ ¤¯Ô˘Ó ‰Â›ÍÂÈ in vitro fiÙÈ ·Ó‚¿˙Ô˘Ó ÙËÓ ·Ú·ÁˆÁ‹ Ù˘ TSST-1 (9).
™˘ÓÈÛÙ¿Ù·È Ë ¯ÔÚ‹ÁËÛË IV ÎÏÈÓ‰·Ì˘Î›Ó˘, ‰ÈfiÙÈ Ë ÎÏÈÓ‰·Ì˘Î›ÓË Î·È ÔÈ ¿ÏϘ Ì·ÎÚÔÏ›‰Â˜ ·Ó·ÛÙ¤ÏÏÔ˘Ó ÙË ‚·ÎÙËÚȉȷ΋ ÚˆÙÂ˚ÓÈ΋ Û‡ÓıÂÛË Î·È ¤¯ÂÈ ·Ô‰Âȯı› fiÙÈ Î·Ù·ÛÙ¤ÏÏÔ˘Ó ÙËÓ ·Ú·ÁˆÁ‹ Ù˘ TSST-1 in vitro, Û ̛· Û˘ÁΤÓÙÚˆÛË ¯·ÌËÏfiÙÂÚË ÙÔ˘ 1/64 Ù˘ ÌÈÎÚfiÙÂÚ˘ ·Ó·ÛÙ·ÏÙÈ΋˜ Û˘ÁΤÓÙÚˆÛ˘ (10). Á) ÛÙËÓ ·ÓÙÈÌÂÙÒÈÛË ÙˆÓ Û˘ÛÙËÌ·ÙÈÎÒÓ ÂΉËÏÒÛÂˆÓ ·fi ÙËÓ ÙÔÍ›ÓË ‹ ÙÔ˘˜ ÌÂÙ·‚È‚·ÛÙ¤˜. ™Â
ÂÈÚ·Ì·Ùfi˙ˆ·, ÙÔ staph-TSS ÌÔÚ› Ó· ÚÔÏËÊı›
Ì ÙË ¯ÔÚ‹ÁËÛË ·ÓıÚÒÈÓ˘ ·ÓÔÛÔÛÊ·ÈÚ›Ó˘, fiÙ·Ó ¯ÔÚËÁËı› ÂÓ‰ÔÊÏ‚›ˆ˜ ÂÓÙfi˜ 30 ˆÚÒÓ ·fi
ÙË ‰Ú¿ÛË Ù˘ TSST-1. ∏ IVIG ÂÚȤ¯ÂÈ ˘„ËϤ˜ Û˘ÁÎÂÓÙÚÒÛÂȘ ·Ó·ÛÙ·ÏÙÈÎÒÓ ·ÓÙÈÛˆÌ¿ÙˆÓ ÂÓ·ÓÙ›ÔÓ
Ù˘ TSST-1 Î·È ¿ÏÏˆÓ ÛÙ·Ê˘ÏÔÎÔÎÎÈÎÒÓ ÂÓÙÂÚÔÙÔ-
ÍÈÓÒÓ (11). ŸÌˆ˜, ÛÙ· ÂÚÈÛÛfiÙÂÚ· ΤÓÙÚ· Ô˘
¤¯ÂÈ ¯ÚËÛÈÌÔÔÈËı›, ¤¯ÂÈ ·Ú·ÙËÚËı› Âȉ›ӈÛË
ÙˆÓ ·ÛıÂÓÒÓ ÌÂÙ¿ ·fi ÌÂÚÈΤ˜ ÒÚ˜ Î·È ‰ÂÓ Û˘ÓÈÛٿٷÈ.
∑ˆÙÈ΋˜ ÛËÌ·Û›·˜ Â›Ó·È Ë ·ÔηٿÛÙ·ÛË ÙÔ˘ ÂÓ‰·ÁÁÂÈ·ÎÔ‡ fiÁÎÔ˘ Î·È Ù˘ ·ÚÙËÚȷ΋˜ ›ÂÛ˘, Ì ÙË ¯ÔÚ‹ÁËÛË ˘ÁÚÒÓ (ÎÚ˘ÛÙ·ÏÏÔÂȉ‹, ÎÔÏÏÔÂȉ‹) Î·È ÈÓÔÙÚfiˆÓ (ÓÙÔ·Ì›ÓË-ÓÙÔÌÔ˘Ù·Ì›ÓË). ™Â ·ÚÎÂÙ¤˜ ÂÚÈÙÒÛÂȘ, Â›Ó·È ·Ó·Áη›Ô˜ Ô Ì˯·ÓÈÎfi˜ ·ÂÚÈÛÌfi˜.
™ÙÚÂÙÔÎÔÎÎÈÎfi TSS
∂ȉËÌÈÔÏÔÁ›·
¶ÂÚÈÁÚ¿ÊËΠÙÔ 1989, ÌÂÙ¿ ·fi ÛÔ‚·Ú¤˜ ÏÔÈÌÒÍÂȘ ·fi ÛÙÚÂÙfiÎÔÎÎÔ Ù˘ ÔÌ¿‰·˜ ∞. ∂ΉËÏÒÓÂÙ·È Û fiϘ ÙȘ ËÏÈ˘, Û˘ÌÂÚÈÏ·Ì‚·ÓÔ̤ӈÓ
Î·È ÙˆÓ ·È‰ÈÒÓ. ™ÙÔÓ ∫·Ó·‰¿, Ô ÂÙ‹ÛÈÔ˜ ‰Â›ÎÙ˘
ÙÔ˘ strep-TSS ÛÙ· ·È‰È¿ Â›Ó·È 0,08 ÂÚÈÙÒÛÂȘ
·Ó¿ 100.000 (12). ∞Ú¯Èο, Ë ·ÓÂÌÔ‚ÏÔÁÈ¿ ıˆڋıËΠˆ˜ Ô ÌÂÁ·Ï‡ÙÂÚÔ˜ ·Ú¿ÁÔÓÙ·˜ ÎÈÓ‰‡ÓÔ˘ ÁÈ·
ÙËÓ ·Ó¿Ù˘ÍË strep-TSS. OÈ ÂÚÈÛÛfiÙÂÚ˜ ÂÚÈÙÒÛÂȘ Â›Ó·È ÛÔÚ·‰ÈΤ˜.
¶·ıÔÁ¤ÓÂÈ·
£ÂˆÚÂ›Ù·È fiÙÈ Â›Ó·È ›‰È· Ì ÂΛÓË ÙÔ˘ staphTSS. ¶·Ú’ fiÏ· ·˘Ù¿, ˘¿Ú¯Ô˘Ó Ô˘ÛÈÒ‰ÂȘ ‰È·ÊÔÚ¤˜ ÙfiÛÔ ÛÙËÓ ·ıÔÁ¤ÓÂÛË, fiÛÔ Î·È ÛÙȘ ÎÏÈÓÈΤ˜
ÂΉËÏÒÛÂȘ (¶›Ó·Î·˜ 2).
¶¤ÓÙ ÙÔ˘Ï¿¯ÈÛÙÔÓ ‰È·ÊÔÚÂÙÈΤ˜ ÛÙÚÂÙÔÎÔÎÎÈΤ˜ Â͈ÙÔ͛Ә ‰ÚÔ˘Ó Û·Ó ˘ÂÚ·ÓÙÈÁfiÓ· in vitro ∞ÏÏ¿ in vivo, Ô ÚfiÏÔ˜ ÙÔ˘˜ Â›Ó·È ÏÈÁfiÙÂÚÔ Î·Ï¿
·ÓÙÈÏËÙfi˜, ·ÊÂÓfi˜ ‰ÈfiÙÈ Ë ·ÚÔ˘Û›· ÙÔ˘˜ ‰ÂÓ Â›-
Ó·È ÛÙÂÓ¿ Û˘Ó‰Â‰Â̤ÓË Ì ÙÔ strep-TSS, ·ÊÂÙ¤ÚÔ˘
ÁÈ·Ù› Ë ÂÏ¿ÙÙˆÛË ÙˆÓ ÎÏÒÓˆÓ V‚ Ô˘ ·Ú·ÙËÚ›ٷÈ
Û ·ÛıÂÓ›˜ Ì strep-TSS, ‰ÂÓ Â›Ó·È ÂȉÈ΋ ÁÈ· η̛· ·fi ·˘Ù¤˜ ÙȘ ÙÔ͛Ә (13). ∂›Û˘, ¿ÏÏÔÈ ·Ú¿ÁÔÓÙ˜ ÓÔÛËÚfiÙËÙ·˜, fiˆ˜ ÔÈ ·ÓÙÈÊ·ÁÔ΢ÙÙ·ÚÈΤ˜ ÚˆÙ½Ó˜ ª ÂÈÊ·Ó›·˜ Î·È ÙÔ ÏÈÔÙ¯ÓÔ˚Îfi
Ô͇ (Ô˘ ¢ԉÒÓÂÈ ÙËÓ ·Ú·ÁˆÁ‹ ÙÔ˘ TNF-a), ÌÔÚ› Ó· Û˘Ì‚¿ÏÔ˘Ó ·Â˘ı›·˜ ÛÙËÓ ÂΉ‹ÏˆÛË ÙÔ˘ strep-TSS. ∞fi ÙËÓ ¿ÏÏË ÌÂÚÈ¿, ·Ó·ÊÔÚ¤˜ ·fi ¢ÂÚÁÂÙÈο ·ÔÙÂϤÛÌ·Ù· Ù˘ ¯ÔÚ‹ÁËÛ˘ IVIG ÛÙÔ strep-TSS, ηıÒ˜ Î·È ÙÔ ÁÂÁÔÓfi˜ fiÙÈ Ë IVIG ÂÚȤ¯ÂÈ ·ÓÙÈÛÒÌ·Ù· Ô˘ ÂÍÔ˘‰ÂÙÂÚÒÓÔ˘Ó ·ÚÎÂÙÔ‡˜
ÛÙÚÂÙÔÎÔÎÎÈÎÔ‡˜ ·Ú¿ÁÔÓÙ˜ ÓÔÛËÚfiÙËÙ·˜, ÂÓÈÛ¯‡Ô˘Ó ÙËÓ ¿Ô„Ë ÁÈ· ÙÔ ÚfiÏÔ ÙˆÓ ÛÙÚÂÙÔÎÔÎÎÈÎÒÓ Â͈ÙÔÍÈÓÒÓ ÛÙËÓ ·ıÔÁ¤ÓÂÛË ÙÔ˘ strep-TSS.
™Â ·ÓÙ›ıÂÛË Ì ÙÔ staph-TSS, ÙÔ strep-TSS Û˘ÓÔ-
Û˘Ó‹ıˆ˜ ·fi ÛÔ‚·Ú‹ ÙÔÈ΋ Ïԛ̈ÍË ·fi ÛÙÚÂÙfiÎÔÎÎÔ ÔÌ¿‰·˜ ∞, Û˘¯Ó¿ Û˘Óԉ¢fiÌÂÓË
‚·ÎÙËÚÈ·ÈÌ›·.
ÂΉËÏÒÛÂȘ
ÂÈÛfi‰Ô˘ ÙÔ˘ ÛÙÚÂÙfiÎÔÎÎÔ˘ ÔÌ¿‰·˜
¿ÁÓˆÛÙË ÛÙÔ 50% ÙˆÓ ÂÚÈÙÒÛÂˆÓ (12). ∞fi ÙËÓ ¿ÏÏË, ηٷÛÙ¿ÛÂȘ fiˆ˜ ¯ÂÈÚÔ˘ÚÁÈΤ˜ ÂÂÌ‚¿ÛÂȘ, ÙÔÎÂÙfi˜, ÏÔÈÌÒÍÂȘ ‰¤ÚÌ·ÙÔ˜ (·ÓÂÌÔ‚ÏÔÁÈ¿) ‹ ÌÈÎÚfi ‰ÂÚÌ·ÙÈÎfi ÙÚ·‡Ì· ÌÔÚÔ‡Ó Ó· ˘¿ÚÍÔ˘Ó ÚÈÓ ÙËÓ ÂÌÊ¿ÓÈÛË strep-TSS.
∂Ï·ÊÚ¿ ÚÔ‰ÚÔÌÈο Û˘ÌÙÒÌ·Ù· ‰È¿ÚÎÂÈ·˜ 13 ËÌÂÚÒÓ ÌÔÚ› Ó· ÂÌÊ·ÓÈÛÙÔ‡Ó ÚÈÓ ÙËÓ ÂΉ‹ÏˆÛË ˘„ËÏÔ‡ ˘ÚÂÙÔ‡. ¶ÔÛÔÛÙfi 80% ÂÚ›Ô˘ ÙˆÓ ÂÚÈÙÒÛˆÓ, ·ÚÔ˘ÛÈ¿˙ÂÈ ÎÏÈÓÈΤ˜ ÂΉËÏÒÛÂȘ ·fi ÏÔÈÌÒÍÂȘ Ì·Ï·ÎÒÓ ÌÔÚ›ˆÓ (΢ÙÙ·Ú›ÙȘ, ¯ÂÈÚÔ˘ÚÁÈΤ˜ ÏÔÈÌÒÍÂȘ, Ì˘ÔÛ›ÙȘ, ÓÂÎÚˆÙÈ΋ ÂÚÈÙÔÓ›ÙȘ).
∆Ô shock Î·È Ë ÔÏ˘ÔÚÁ·ÓÈ΋ ·Ó¿ÚÎÂÈ· ›ӷÈ
·ÔÙ¤ÏÂÛÌ· ‰‡Ô ·Ú·ÁfiÓÙˆÓ (6): ·) Ù˘ ·Â˘ı›·˜ ‰Ú¿Û˘ Ù˘ ÙÔ͛Ӣ Î·È ÙˆÓ ÌÂÙ·‚È‚·ÛÙÒÓ ÛÙ· ·ÙÙ·Ú· Î·È Ù˘ ÈÛÙÈ΋˜ ÈÛ¯·ÈÌ›·˜, Ô˘ ·Ú¯Èο
¶›Ó·Î·˜ 2. ™˘ÁÎÚÈÙÈο ¯·Ú·ÎÙËÚÈÛÙÈο ÙˆÓ ÙÔÍÈÎÒÓ shock Û˘Ó‰ÚfïÓ
Strep TSSStaph TSS
∆Ô͛Ә
speA, speB, speC ÛÙÚÂÙÔÎÔÎÎÈο ˘ÂÚ·ÓÙÈÁfiÓ·TSST-1, ÂÓÙÂÚÔÙÔ͛Ә ∞ÓÔÛÔÏÔÁ›· ∂Ï¿ÙÙˆÛË ÎÏÒÓÔ˘ V‚∞‡ÍËÛË ÎÏÒÓÔ˘ V‚ ¶Úfi‰ÚÔÌ· Û˘ÌÙÒÌ·Ù· °Ú›Ë˜-likeŒÌÂÙÔ˜-‰È¿ÚÚÔÈ· ¢È¿ÚÎÂÈ· Úfi‰ÚÔÌˆÓ Û˘ÌÙˆÌ¿ÙˆÓ ∞fi ÒÚ˜ ̤¯ÚÈ Ë̤Ú˜flÚ˜ ™Ô‚·ÚfiÙËÙ· Úfi‰ÚÔÌˆÓ Û˘ÌÙˆÌ¿ÙˆÓ + +++ ∆ÔÈ΋ Ïԛ̈ÍË ++++ (.¯. Ó¢ÌÔÓ›·, Ïԛ̈ÍË ÔÛÙÒÓ, ΢ÙÙ·Ú›ÙȘ, ÓÂÎÚˆÙÈ΋ ÂÚÈÙÔÓ›ÙȘ)
£ÂÙÈ΋ ·ÈÌÔηÏÏȤÚÁÂÈ· +++¶fiÓÔ˜ ÛÙËÓ ÂÓÙfiÈÛË Ù˘ Ïԛ̈͢ ++++ ∂Í¿ÓıËÌ· OÛÙÚ·ÎÈ҉˜∂Ú˘ıÚÔ‰ÂÚÌ›· Shock ¢‡ÛÎÔÏÔ Ó· ·ÓÙÈÌÂÙˆÈÛÙ›∞ÓÙÈÌÂÙˆ›˙ÂÙ·È
¶ÔÏ˘ÔÚÁ·ÓÈ΋ ·Ó¿ÚÎÂÈ· ++++ ¢È·Ù·Ú·¯¤˜ ‹Í˘ ++++
£ÓËÙfiÙËÙ·
À„Ëϋ÷ÌËÏ‹
ÔÊ›ÏÂÙ·È ÛÙËÓ ·ÒÏÂÈ· ÙÔ˘ ÙfiÓÔ˘ ÙˆÓ ·ÁÁ›ˆÓ Î·È ‚) ÛÙÔ ÂÎÙÂٷ̤ÓÔ ‰È¿ÌÂÛÔ Ô›‰ËÌ· Ô˘ Û˘ÌȤ˙ÂÈ
Î·È ÚÔηÏ› ‰˘ÛÏÂÈÙÔ˘ÚÁ›· ÙˆÓ ·ÁÁ›ˆÓ.
∆Ș ÂfiÌÂÓ˜ 24-48 ÒÚ˜ ÌÔÚ› Ó· ·ÚÔ˘ÛÈ·-
ÛÙÔ‡Ó ARDS (ÏfiÁˆ Ù˘ ÙÚȯÔÂȉÈ΋˜ ‰È·Ê˘Á‹˜ η-
Ù¿ ÙË ¯ÔÚ‹ÁËÛË ˘ÁÚÒÓ ·Ó·Ï‹ÚˆÛ˘), Ì˘ÔηÚ-
‰ÈÔ¿ıÂÈ· ¢∂¶ Î·È ÓÂÊÚÈ΋ ·Ó¿ÚÎÂÈ· (ÓÂÊÚÈ΋
Î·È ÚÔÓÂÊÚÈ΋). ∏ ıÓËÙfiÙËÙ· ·Ó¤Ú¯ÂÙ·È Û ÔÛÔ-
ÛÙfi 30-70%.
¢È·ÁÓˆÛÙÈο ÎÚÈÙ‹ÚÈ· ÁÈ· ÙÔ strep-TSS (8)
1. ∞ÔÌfiÓˆÛË ÛÙÚÂÙfiÎÔÎÎÔ˘ ÔÌ¿‰·˜ ∞: ·. ·fi Ê˘ÛÈÔÏÔÁÈο ÛÙ›ڷ ÂÛÙ›· (.¯. ·›Ì·, ÂÁÎÂ-
Ê·ÏÔÓˆÙÈ·›Ô ˘ÁÚfi, ÂÚÈÙÔÓ·˚Îfi ˘ÁÚfi, ‚ÈÔ„›·
ÈÛÙÒÓ, ¯ÂÈÚÔ˘ÚÁÈÎfi ÙÚ·‡Ì·) ηÈ
‚. ·fi Ì›· fi¯È ÛÙ›ڷ ÂÛÙ›· (.¯. Ê¿Ú˘ÁÁ·˜, ÂÈÊ·-
ÓÂȷ΋ ‰ÂÚÌ·ÙÈ΋ ‚Ï¿‚Ë).
2. ∫ÏÈÓÈο ÛËÌ›· Ô˘ ‰Â›¯ÓÔ˘Ó ÙË ÛÔ‚·ÚfiÙËÙ·
ÙÔ˘ Û˘Ó‰ÚfiÌÔ˘ ·ÔÙÂÏÔ‡Ó:
·. Ë ˘fiÙ·ÛË (Û˘ÛÙÔÏÈ΋ ›ÂÛË <90 mmHg ÛÙÔ˘˜
ÂÓ‹ÏÈΘ ‹ <5Ë ÂηÙÔÛÙÈ·›· ı¤ÛË ÛÙ· ·È‰È¿) ηÈ
‚. 2 ‹ ÂÚÈÛÛfiÙÂÚ· ·fi Ù· ·ÎfiÏÔ˘ı·: i) ¡ÂÊÚÈ΋ ·Ó¿ÚÎÂÈ·: ÎÚ·ÙÈÓ›ÓË >2 mg/dl (ÙÈ-
̤˜ >2Ï¿ÛÈÔ ÙˆÓ Ê˘ÛÈÔÏÔÁÈÎÒÓ)
ii) ¢È·Ù·Ú·¯¤˜ ‹Í˘: ∞ª¶ <100.000/mm3 ‹
¢∂¶
iii) ◊·Ú: ·‡ÍËÛË SGOT, SGPT ‹ ÔÏÈ΋˜ ¯ÔÏÂ-
Ú˘ıÚ›Ó˘ (ÙÈ̤˜ >2Ï¿ÛÈÔ ÙˆÓ Ê˘ÛÈÔÏÔÁÈÎÒÓ)
iv) ARDS
v) ∂Í¿ÓıËÌ· ÎËÏȉ҉˜, Ô˘ ÌÔÚ› Ó· ÂÍÂÏÈ-
¯ı› Û ·ÔϤÈÛË vi) ¡¤ÎÚˆÛË Ì·Ï·ÎÒÓ ÌÔÚ›ˆÓ, ÂÚÈÏ·Ì‚¿ÓÔ-
ÓÙ·˜ ÓÂÎÚˆÙÈ΋ ÂÚÈÙÔÓ›Ùȉ· ‹ Ì˘ÔÛ›Ùȉ· ‹ Á¿Á-
ÁÚ·ÈÓ·.
∏ ‰È¿ÁÓˆÛË Ù›ıÂÙ·È Ì ‚‚·ÈfiÙËÙ· fiÙ·Ó ÂÚÈ-
Ï·Ì‚¿ÓÔÓÙ·È Ù· ÎÚÈÙ‹ÚÈ· 1· Î·È 2 (· Î·È ‚), ÂÓÒ Ë
‰È¿ÁÓˆÛË Â›Ó·È Èı·Ó‹ fiÙ·Ó ÂÚÈÏ·Ì‚¿ÓÔÓÙ·È Ù·
ÎÚÈÙ‹ÚÈ· 1‚ Î·È 2 (· Î·È ‚).
£Âڷ›·
OÈ ·Ú¯¤˜ Ù˘ ·ÓÙÈÌÂÙÒÈÛ˘ ÙÔ˘ strep-TSS ›ӷÈ
›‰È˜ Ì ÂΛӘ ÙÔ˘ staph-TSS. ∏ Ì˯·ÓÈ΋ ·Ê·›ÚÂÛË ÌÔÏ˘Ṳ̂ÓÔ˘ ͤÓÔ˘ ÛÒÌ·-
ÙÔ˜ Î·È Ë ·ÚÔ¯¤Ù¢ÛË Ù˘ ÌÔÏ˘Ṳ̂Ó˘ ÂÚÈÔ¯‹˜
¤¯Ô˘Ó Ôχ ÌÂÁ¿ÏË ÛËÌ·Û›·, ÏfiÁˆ Ù˘ ·ÚÔ˘Û›·˜
˘„ËÏ‹˜ Û˘ÁΤÓÙÚˆÛ˘ ÙˆÓ ÌÈÎÚÔÔÚÁ·ÓÈÛÌÒÓ. ™˘ÓÈÛÙ¿Ù·È ·ÓÙÈÌÈÎÚԂȷ΋ ıÂڷ›· Ì ¯ÔÚ‹-
ÁËÛË IV ‚-Ï·ÎÙ¿Ì˘ Î·È ÎÏÈÓ‰·Ì˘Î›Ó˘. ∆Ô ÛÎÂÙÈ-
Îfi Ù˘ ¯Ú‹Û˘ Ù˘ ÎÏÈÓ‰·Ì˘Î›Ó˘ Â›Ó·È ÔÏ˘·Ú·-
ÁÔÓÙÈÎfi Î·È ÂÚÈÏ·Ì‚¿ÓÂÈ ÙËÓ ·Ó·ÛÙÔÏ‹ Ù˘ ·Ó¿-
Ù˘Í˘ ÙÔ˘ ÛÙÚÂÙfiÎÔÎÎÔ˘ Û ˘„ËÏ‹ ˘ÎÓfiÙËÙ·, ηıÒ˜ ÔÈ ‚-Ï·Îٿ̘ Â›Ó·È ÏÈÁfiÙÂÚÔ ·ÔÙÂÏÂÛÌ·ÙÈΤ˜ (14), ÙËÓ Î·Ù·ÛÙÔÏ‹ Ù˘ ·Ú·ÁˆÁ‹˜ Ù˘ ‚·ÎÙËÚȉȷ΋˜ ÙÔ͛Ӣ Î·È ÙËÓ Â˘ÎÔÏ›· ‚·ÎÙËÚȉȷ΋˜ Ê·ÁÔ΢ÙÙ¿ÚˆÛ˘ ·fi ÙËÓ ·Ó·ÛÙÔÏ‹ Ù˘ Û‡ÓıÂÛ˘
Ù˘ ÚˆÙ½Ó˘ ª. ™˘ÓÈÛٿٷÈ, ›Û˘, ¯ÔÚ‹ÁËÛË IVIG ÂÓ‰ÔÊÏ‚›ˆ˜, Ë ÔÔ›· ‚ÂÏÙÈÒÓÂÈ ÙËÓ ¤Î‚·ÛË ÙÔ˘ strepTSS (11).
¶ÚÔʇϷÍË ∏ ÂÊ·ÚÌÔÁ‹ ·ÓÙÈÌÈÎÚԂȷ΋˜ ·ÁˆÁ‹˜ ÓˆÚ›˜, ÛÂ
¤ÓÙÔÓ· ÌÔÏ˘Ṳ̂Ó˜ ‰ÂÚÌ·ÙÈΤ˜ ‚Ï¿‚˜ ·fi ·ÓÂÌÔ‚ÏÔÁÈ¿, ηıÒ˜ Î·È Ë Â˘ÂÚÁÂÙÈ΋ ·ÓÔÛÔÔ›ËÛË ÁÈ· ÙËÓ ·ÓÂÌÔ‚ÏÔÁÈ¿, ÌÔÚ› Ó· ÚÔÏ¿‚Ô˘Ó ÏÔÈÌÒÍÂȘ ·fi ÛÙÚÂÙfiÎÔÎÎÔ ÔÌ¿‰·˜ ∞, ηıÒ˜ Î·È ÙÔ strepTSS. ÿÛˆ˜, Û ÎÏÂÈÛÙfi ·ÎÏÔ, ı· ÌÔÚÔ‡Û ӷ ‚ÔËı‹ÛÂÈ Ë ¯ËÌÂÈÔÚÔʇϷÍË, ¯ˆÚ›˜ ·ÎfiÌË Ó· Û˘ÛÙ‹ÓÂÙ·È Â˘Ú‡Ù·Ù·.
µÈ‚ÏÈÔÁÚ·Ê›·
1. Broome CV. Epidemiology of toxic shock syndrome in the United States: overview. Rev Infect Dis 1989;11 (Suppl 1):S14-S21.
2. Jacobson JA, Kasworm EM, Reiser RF, Bergdoll MS. Low incidence of toxic shock syndrome in children with staphylococcal infection. Am J Med Sci 1987;294:403-407.
3. Lee VT, Chang AH, Chow AW. Detection of staphylococcal enterotoxin B among toxic shock syndrome (TSS)- and non-TSS-associated Staphylo-coccusaureus isolates. J Infect Dis 1992;166:911-915.
4. Parsonnet J. Nonmenstrual toxic shock syndrome: new insights into diagnosis, pathogenesis, and treatment. Curr Clin Top Infect Dis 1996;16:1-20.
5. Chesney PJ, Davis JP. Toxic shock syndrome. In: Feigin RD, Cherry JD, editors. Textbook of Pediatric Infectious Diseases. 4th ed. Philadelphia: Saunders; 1998. p. 830-852.
6. µ·ÛÈÏfiÔ˘ÏÔ˜ ∞. ™‡Ó‰ÚÔÌÔ ÙÔÍÈÎÔ‡ ÛÙ·Ê˘ÏÔÎÔÎÎÈÎÔ‡ shock ÛÙ· ·È‰È¿. (¶ÂÚ›ÏË„Ë). 5o ™ÂÌÈÓ¿ÚÈÔ ∂›ÁÔ˘Û·˜ ∂ÓÙ·ÙÈ΋˜ ¶·È‰È·ÙÚÈ΋˜. ªÔÓ¿‰· ∂ÓÙ·ÙÈ΋˜ £Âڷ›·˜ “¶. & ∞. ∫˘ÚÈ·ÎÔ‡”; 1991 ™Â٤̂ÚÈÔ˜; ∞ı‹Ó·; 1991. ÛÂÏ. 2-6.
7. Bergdoll MS, Crass BA, Reiser RF, Robbins RN, Davis JP. A new staphylococcal enterotoxin, enterotoxin F, associated with toxic shock syndrome Staphylococcus aureus isolates. Lancet 1981;1:1017-1021.
8. Spentzas T. Index of suspicion. Case 1. Toxic shock syndrome. Pediatr Rev 1999;20:199-201.
9. Kernodle DS, McGraw PA, Barg NL, Menzies BE, Voladri RK, Harshman S. Growth of Staphylococcus aureus with nafcillin in vitro induces alpha-toxin production and increases the lethal activity of sterile broth filtrates in a murine model. J Infect Dis 1995;172:410-419.
10. Schlievert PM, Kelly JA. Clindamycin-induced suppression of toxic shock syndrome-associated exotoxin production. J Infect Dis 1984;149:471.
11. Kaul R, McGeer A, Norrby-Teglund A, Kotb M, Schwartz B, O’Rourke K et al. Intravenous immunoglobulin therapy for streptococcal toxic shock syndrome-a comparative observational study. The Canadian Streptococcal Study Group. Clin Infect Dis 1999;28:800-807.
12. Laupland KB, Davies HD, Low DE, Schwartz B, Green K, McGeer A. Invasive group A streptococcal disease in
children and association with varicella-zoster virus infection. Ontario Group A Streptococcal Study Group. Pediatrics 2000;105:60.
13. Watanabe-Ohnishi R, Low DE, McGeer A, Stevens DL, Schlievert PM, Newton D et al. Selective depletion of V betabearing T cells in patients with severe invasive group A streptococcal infections and streptococcal toxic shock syndrome. Ontario Streptococcal Study Project. J Infect Dis 1995;171:74-84.
14. Stevens DL, Yan S, Bryant AE. Penicillin-binding protein expression at different growth stages determines penicillin efficacy in vitro and in vivo: an explanation for the inÔculum effect. J Infect Dis 1993;167:1401-1405.
15. Schlievert PM, Shands KN, Dan BB, Schmid GP, Nishimura RD. Identification and characterization of an exotoxin from Staphylococcus aureus associated with toxic-shock syndrome. J Infect Dis 1981;143:509-516.
16. Vergeront JM, Stolz SJ, Crass BA, Nelson DB, Davis JP,
Begdoll MS. Prevalence of serum antibody to staphylococcal enterotoxin F among Wisconsin residents: implications for toxic shock syndrome. J Infect Dis 1983;148:692-698.
17. Notermans S, van Leeuwen WJ, Dufrenne J, Tips PD. Serum antibodies to enterotoxins produced by Staphylococcus aureus with special reference to enterotoxin F and toxic shock syndrome. J Clin Microbiol 1983;18:1055-1060.
HÌÂÚÔÌËÓ›· ˘Ô‚ÔÏ‹˜: 15-07-2002
HÌÂÚÔÌËÓ›· ¤ÁÎÚÈÛ˘: 14-02-2003
¢È‡ı˘ÓÛË ·ÏÏËÏÔÁÚ·Ê›·˜: ∞. µ·ÛÈÏfiÔ˘ÏÔ˜
ªÔÓ¿‰· ∂ÓÙ·ÙÈ΋˜ £Âڷ›·˜ ¶·È‰ÈÒÓ
¶·›‰ˆÓ “¶. & ∞. ∫˘ÚÈ·ÎÔ‡”, ∞ı‹Ó·
Mycoplasma pneumoniae Î·È Chlamydia pneumoniae
™ÎÔfi˜ - ÀÏÈÎfi Î·È Ì¤ıÔ‰ÔÈ: °È· ÙÔÓ Î·ıÔÚÈÛÌfi ÙÔ˘ ÚfiÏÔ˘
ÙÔ˘ ª. pneumoniae Î·È ÙÔ˘ C. pneumoniae ÛÙËÓ ·ÓÙȉڷ-
ÛÙÈ΋ ÓfiÛÔ ÙˆÓ ·ÂÚ·ÁˆÁÒÓ, ÂÍÂÙ¿ÛÙËÎ·Ó 71 ·È‰È¿ ËÏÈΛ·˜ 2-14 ÂÙÒÓ Ì ¤Ó· ÂÂÈÛfi‰ÈÔ Û˘ÚÈÁÌÔ‡ Î·È 80 ˘ÁÈ‹ ·È‰È¿
·ÓÙ›ÛÙÔȯ˘ ËÏÈΛ·˜. ∂Ï‹ÊıËÛ·Ó ‰Â›ÁÌ·Ù· ÔÚÔ‡ ÁÈ· ÙÔÓ
ÚÔÛ‰ÈÔÚÈÛÌfi ÙˆÓ ÂȤ‰ˆÓ ÂȉÈÎÒÓ ·ÓÙÈۈ̿وÓ, ηıÒ˜
Î·È ÚÈÓÔÊ·Ú˘ÁÁÈÎfi ¤ÎÎÚÈÌ· ÁÈ· ÙËÓ ·Ó›¯Ó¢ÛË ‰ÂÛÔ͢ÚÈ‚Ô-
ÓÔ˘ÎÏÂ˚ÎÔ‡ ÔͤԘ ÙÔ˘ M. pneumoniae Î·È ÙÔ˘ C. pneumoniae, ηٿ ÙËÓ ÂÈÛ·ÁˆÁ‹ ÙˆÓ ·ÛıÂÓÒÓ Î·È 4-6 ‚‰ÔÌ¿‰Â˜ ÌÂÙ¿. ŸÏ· Ù· ·È‰È¿ ÌÂ Û˘ÚÈÁÌfi ·ÓÙÈÌÂÙˆ›ÛÙËÎ·Ó Ì ηıÔÚÈṲ̂ÓË ·ÁˆÁ‹, Ô˘ ÂÚÈÂÏ¿Ì‚·Ó ÂÈÛÓÂfiÌÂÓ· ÎÔÚÙÈÎÔÛÙÂÚÔÂȉ‹ Î·È ‚ÚÔÁ¯Ô‰È·ÛÙ·ÏÙÈο ÁÈ· 5-7 Ë̤Ú˜. ŸÙ·Ó, ˘fi ÙËÓ ÎÚ›ÛË ÙÔ˘ ÂÊËÌÂÚ‡ÔÓÙÔ˜ È·ÙÚÔ‡, ÚÔÛÙ¤ıËΠ·ÓÙÈ‚ÈÔÙÈÎfi, ÂÈϤ¯ıËÎÂ Ë ÎÏ·ÚÈıÚÔÌ˘Î›ÓË 15 mg/kg ۈ̷ÙÈÎÔ‡ ‚¿ÚÔ˘˜ ÁÈ· 10 Ë̤Ú˜.
∞ÔÙÂϤÛÌ·Ù·: OÍ›˜ ·Ó·Ó¢ÛÙÈΤ˜ ÏÔÈÌÒÍÂȘ ·fi M. pneumoniae Î·È C. pneumoniae ÂÓÙÔ›ÛÙËÎ·Ó Ôχ ÈÔ Û˘¯Ó¿ Û ·È‰È¿ ÌÂ Û˘ÚÈÁÌfi, Û ۯ¤ÛË Ì ٷ ·È‰È¿ Ù˘ ÔÌ¿‰·˜ ÙˆÓ Ì·ÚÙ‡ÚˆÓ. ™Â ·ÛıÂÓ›˜ Ì Ïԛ̈ÍË ÙÔ˘ ·Ó·Ó¢ÛÙÈÎÔ‡ ÂÍ·ÈÙ›·˜ ÂÓfi˜ ·fi ÙÔ˘˜ ‰‡Ô ·˘ÙÔ‡˜ ·ıÔÁfiÓÔ˘˜ ÌÈÎÚÔÔÚÁ·ÓÈÛÌÔ‡˜, ÙÔ ÈÛÙÔÚÈÎfi ·ÓÂÈÏËÌ̤ӈÓ
·˘Ù¿ Ì ÔÍ›· Ïԛ̈ÍË ·fi M. pneumoniae Î·È C. pneumoniae ·ÚÔ˘Û›·Û·Ó ÛËÌ·ÓÙÈο
ÙˆÓ ÂÂÈÛÔ‰›ˆÓ Û˘ÚÈÁÌÔ‡, Û ۯ¤ÛË Ì ·˘Ù¿ ¯ˆÚ›˜ Ïԛ̈ÍË ·fi Ù· ·Ú·¿Óˆ ·ıÔÁfiÓ· (p=0,03).
™˘ÌÂÚ¿ÛÌ·Ù·: ∆· ·ÔÙÂϤÛÌ·Ù· ·˘Ù¿ ÛËÌ·ÙÔ‰ÔÙÔ‡Ó Ì›· ηٷʷӋ Û¯¤ÛË ÌÂٷ͇ ÙÔ˘ M. pneumoniae Î·È ÙÔ˘ C. pneumoniae Î·È ÙˆÓ ÂÂÈÛÔ‰›ˆÓ Û˘ÚÈÁÌÔ‡ Û ·È‰È¿, ΢ڛˆ˜ fiÙ·Ó ·˘Ù¿ Â›Ó·È Â·ÓÂÈÏËÌ̤ӷ, ηıÒ˜ Î·È ÙËÓ Èı·Ó‹ ‚ÂÏÙ›ˆÛË Ù˘ ÔÚ›·˜ Ù˘ ·ÓÙȉڷÛÙÈ΋˜ ÓfiÛÔ˘ ÙˆÓ ·ÂÚ·ÁˆÁÒÓ Û ·È‰È¿ Ì ·ÓÙÈÌÂÙÒÈÛË Ù˘ ÔÍ›·˜ Ïԛ̈͢ ·fi M. pneumoniae ηÈ/‹ C. pneumoniae
1Esposito S, Blasi F, Arosio C, Fioravanti L, Fagetti L, Droghetti R et al
Importance of acute Mycoplasma pneumoniae and Chlamydia pneumoniae infections in children with wheezing
Eur Respir J 2000;16:1142-1146
∂ƒ∂À¡∏∆π∫∏
¯Ú‹ÛË Ù˘ ÙÔÈÚ·Ì¿Ù˘ ÛÙË ıÂڷ›· ·ÓıÂÎÙÈÎÒÓ ÂÈÏË„ÈÒÓ
·È‰ÈÒÓ Î·È ÂÊ‹‚ˆÓ
M. ∆˙Ô‡ÊË, M. ÷ڛÛË, I. ¶·ÛÈ¿˜, A. ™ÈÒÌÔ˘, A. ™È·ÌÔÔ‡ÏÔ˘ - ª·˘Ú›‰Ô˘, Z. ¶··‰ÔÔ‡ÏÔ˘ - ∫Ô˘ÏÔ˘Ì‹
The use of topiramate in the treatment of drug-resistant epilepsiesin children and adolescents M. Tzoufi, M. Charisi, I. Pasias, A. Siomou, A. Siamopoulou - Mavridou, Z. Papadopoulou - Couloumbis
¶ÂÚ›ÏË„Ë: ∏ ÙÔÈÚ·Ì¿ÙË Â›Ó·È ¤Ó· Ó¤Ô ·ÓÙÈÂÈÏËÙÈÎfi Ê¿ÚÌ·ÎÔ (∞∂º) Ô˘ ¯ÔÚËÁÂ›Ù·È Û ÂÓ‹ÏÈΘ Î·È ·È‰È¿ ËÏÈΛ·˜ ≥2 ÂÙÒÓ, ˆ˜ Û˘ÌÏËڈ̷ÙÈ΋ ıÂڷ›· ÛÙËÓ ·ÓıÂÎÙÈ΋ ÛÙ· Ê¿Ú̷η ÂÛÙȷ΋
ÂÈÏË„›·. º·›ÓÂÙ·È, fï˜, fiÙÈ ÌÔÚ› Ó· Â›Ó·È ¯Ú‹ÛÈÌË Î·È Û ·È‰È¿ Ì ÔÏÏ·ÏÔ‡˜ Ù‡Ô˘˜ ÎÚ›ÛˆÓ,
ÛÙÔ Û‡Ó‰ÚÔÌÔ Lennox-Gastaut ‹ Û ·È‰È¿
Ì ÂÈÏË„›Â˜ ·ÓıÂÎÙÈΤ˜ Û ¿ÏÏ· ∞∂º. ™ÎÔfi˜ Ù˘
·ÚÔ‡Û·˜ ÌÂϤÙ˘ ‹Ù·Ó Ë ·ÍÈÔÏfiÁËÛË Ù˘ ·ÔÙÂ-
ÏÂÛÌ·ÙÈÎfiÙËÙ·˜ Î·È Ù˘ ·ÛÊ¿ÏÂÈ·˜ ÙÔ˘ Ê·ÚÌ¿ÎÔ˘, ˆ˜ Û˘ÌÏËڈ̷ÙÈ΋˜ ·ÁˆÁ‹˜, Û ·È‰È¿ Ì ·ÓıÂ-
ÎÙÈΤ˜ ÂÈÏË„›Â˜. H ·Ó·‰ÚÔÌÈ΋ ·˘Ù‹ ÌÂϤÙË ·ÊÔ-
ÚÔ‡Û 17 ·ÛıÂÓ›˜ (6 ÎÔÚ›ÙÛÈ· Î·È 11 ·ÁfiÚÈ·), ËÏÈ-
Λ·˜ 4,5-19 ÂÙÒÓ (̤ÛË ËÏÈΛ·: 10,4 ¤ÙË), Ì ̷ÎÚfi-
¯ÚÔÓË Î·È ·ÓıÂÎÙÈ΋ ÛÙ· Ê¿Ú̷η ÂÈÏË„›· (̤ÛË
‰È¿ÚÎÂÈ· ÓfiÛÔ˘: 6,9 ¤ÙË). ªÂ ‚¿ÛË ÙËÓ Ù·ÍÈÓfiÌËÛË
Ù˘ ¢ÈÂıÓÔ‡˜ ŒÓˆÛ˘ ηٿ Ù˘ ∂ÈÏË„›·˜, 6 ·ÛıÂ-
Ó›˜ ÂÌÊ¿ÓÈ˙·Ó ÁÂÓÈÎÂ˘Ì¤ÓË ÂÈÏË„›· (3 Û˘Ìو̷-
ÙÈ΋, 3 ÎÚ˘ÙÔÁÂÓ‹) Î·È 11 ÂÛÙȷ΋ (8 Û˘Ìو̷ÙÈ΋, 4 ÎÚ˘ÙÔÁÂÓ‹). ∞fi ·˘ÙÔ‡˜, 8 ÂÌÊ¿ÓÈ˙·Ó Û‡ÓıÂÙ˜ ÂÛÙȷΤ˜ ÎÚ›ÛÂȘ, 3 ÂÛÙȷΤ˜ ÎÚ›ÛÂȘ (2 ÌÂ
‰Â˘ÙÂÚÔ·ı‹ ÁÂӛ΢ÛË), 4 Û‡Ó‰ÚÔÌÔ LennoxGastaut (1 ·Ú¯Èο Ì ‚ÚÂÊÈÎÔ‡˜ Û·ÛÌÔ‡˜), 1 Ì˘ÔÎÏÔÓÈΤ˜ ·Ê·ÈÚ¤ÛÂȘ Î·È 1 ÁÂÓÈÎÂ˘Ì¤ÓÔ˘˜ ÙÔÓÈÎÔÎÏÔÓÈÎÔ‡˜ Û·ÛÌÔ‡˜. ŸÏÔÈ ÔÈ ·ÛıÂÓ›˜ ÂÏ¿Ì‚·Ó·Ó ·fi 1 ¤ˆ˜ 4 ¿ÏÏ· ·ÓÙÈÂÈÏËÙÈο Ê¿Ú̷η. ∏
ÙÔÈÚ·Ì¿ÙË ÚÔÛÙ¤ıËΠÛÙ· Ê¿Ú̷η Ô˘ ‹‰Ë
¤·ÈÚÓ·Ó ÔÈ ·ÛıÂÓ›˜, Û ‰fiÛË ¤Ó·Ú͢ 1 mg/kg/24 h Î·È ·˘Í‹ıËΠÛÙ·‰È·Î¿, ·Ó¿ÏÔÁ· Ì ÙËÓ ·ÓÙ·fi-
ÎÚÈÛË ÙˆÓ ·ÛıÂÓÒÓ ÛÂ 3-10 mg/kg/24 h. ∏ ·Ú·ÎÔ-
ÏÔ‡ıËÛË ÙˆÓ ·ÛıÂÓÒÓ ‰È‹ÚÎÂÛ 5-15 Ì‹Ó˜. ªÂÙ¿ ÙÔ ‰È¿ÛÙËÌ· ·˘Ùfi, ÙËÓ ·ÁˆÁ‹ Û˘Ó¤¯È˙·Ó 13/17 ·ÛıÂÓ›˜, ÂÓÒ ‰È·ÎfiËΠ۠4 ·ÛıÂÓ›˜ (23,5%), ÏfiÁˆ ÌË ‚ÂÏÙ›ˆÛ˘ (3) ‹ Âȉ›ӈÛ˘ (1) Ù˘ Û˘¯ÓfiÙËÙ·˜
∆Ô̤·˜ ÀÁ›·˜ ÙÔ˘ ¶·È‰ÈÔ‡, ¶·È‰È·ÙÚÈ΋ ∫ÏÈÓÈ΋ ¶·ÓÂÈÛÙËÌÈ·ÎÔ‡
Abstract: Topiramate is a novel anti-epileptic drug (AED) that is used in adults and in children aged ≥2 years, as adjunctive treatment of focal epilepsy that is resistant to drugs. However, it seems that it may also be useful in children with multiple types of epilepsy, such as Lennox-Gastaut syndrome or in children with epilepsies that are resistant to other anti-epileptic drugs. The aim of the present study was the evaluation of effectiveness and safety in the use of the drug, as adjunctive treatment, in children with drug-resistant epilepsy. In this retrospective study included 17 patients (6 girls and 11 boys), aged between 4.5-19 years (median: 10.4 years) with long-term and drugresistant epilepsy (median disease duration: 6.9 years). Based on the classification of International League Against Epilepsy, 6 had generalized epilepsy (3 symptomatic, 3 cryptogenic) and 11 had focal epilepsy (8 symptomatic, 4 cryptogenic). Of these, 8 had complex partial seizures, 3 had partial seizures (2 with secondary generalization), 4 had Lennox-Gastaut syndrome (1 suffered primarily from infantile spasms), 1 suffered from myoclonic absences and 1 from generalized tonic-clonic seizures. All patients received 1-3 AEDs. Topiramate was added to the treatment regimen that the patients were already taking, at a starting dose of 1 mg/kg/24 h and was gradually increased - depending on the patient’s response - to 3.0-10 mg/kg/24 h. In 11/17 patients (64.7%) demonstrated ≥50% decrease in seizure activity and 6/17 patients (35.2%) became seizure free. Effectiveness was observed in various types of seizures and types of epilepsy especially in any type and etiology focal epilepsy. Adverse effects
Department of Child Health, Pediatric Clinic, University Hospital of Ioannina
ÙˆÓ ÂÈÏËÙÈÎÒÓ ÎÚ›ÛÂˆÓ Û ÔÛÔÛÙfi ≥50% ÂÌÊ¿ÓÈÛ·Ó 11/17 ·ÛıÂÓ›˜ (64,7%), ÂÓÒ 6 ·fi ·˘ÙÔ‡˜ ··ÏÏ¿¯ÙËÎ·Ó Ï‹Úˆ˜ (35,2%). ∞ÔÙÂÏÂÛÌ·ÙÈÎfiÙËÙ· ÙÔ˘ Ê·ÚÌ¿ÎÔ˘ ·Ú·ÙËÚ‹ıËΠ۠ÔÈΛÏÔ˘˜ Ù‡Ô˘˜ ÂÈÏËÙÈÎÒÓ ÎÚ›ÛÂˆÓ Î·È Û˘Ó‰ÚfïÓ, ȉȷ›ÙÂÚ· ÛÙËÓ ÔÔÈ·Û‰‹ÔÙ ÌÔÚÊ‹˜ Î·È ·ÈÙÈÔÏÔÁ›·˜ ÂÛÙȷ΋ ÂÈÏË„›·. ¶·ÚÂÓ¤ÚÁÂȘ ÂÌÊ¿ÓÈÛ·Ó
10/17 ·ÛıÂÓ›˜ (58,8%): 4 ·ÒÏÂÈ· ‚¿ÚÔ˘˜ ηÈ
·ÓÔÚÂÍ›·, 4 ÂÈıÂÙÈÎfiÙËÙ· Î·È 2 ˘ÓËÏ›· Î·È ‰˘ÛÎÔϛ˜ Û˘ÁΤÓÙÚˆÛ˘. ™˘ÌÂÚ·ÛÌ·ÙÈο, Ë ÙÔÈÚ·Ì¿ÙË ·Ô‰Â›¯ıËΠ·ÚÎÂÙ¿ ·ÔÙÂÏÂÛÌ·ÙÈ΋ ηÈ
·ÛÊ·Ï‹˜ ˆ˜ Û˘ÌÏËڈ̷ÙÈ΋ ıÂڷ›· Û 11/17
·È‰È¿ Î·È ÂÊ‹‚Ô˘˜, Ì ¤Ó· ÌÂÁ¿ÏÔ Â‡ÚÔ˜ ·ÓıÂÎÙÈÎÒÓ ÂÈÏË„ÈÒÓ, ÙfiÛÔ ÎÚ˘ÙÔÁÂÓÒÓ fiÛÔ Î·È Û˘-
Ìو̷ÙÈÎÒÓ. ¶·Ú·ÙËÚ‹ıËΠ·ÓÙ·fiÎÚÈÛË Û ÔÛÔÛÙfi ≥50% ÛÙÔ 64,7% ÙˆÓ ·È‰ÈÒÓ Ù˘ ÌÂϤÙ˘.
∆Ô Ê¿ÚÌ·ÎÔ ‹Ù·Ó ÁÂÓÈο ηÏÒ˜ ·ÓÂÎÙfi Î·È ÔÈ ·ÚÂÓ¤ÚÁÂȘ Ô˘ ·ÚÔ˘ÛÈ¿ÛÙËÎ·Ó ÛÙÔ 58,8% ‹Ù·Ó
ˆ˜ › ÙÔ Ï›ÛÙÔÓ ‹È˜ Î·È ·ÚÔ‰ÈΤ˜. ∆¤ÛÛÂÚȘ
·ÛıÂÓ›˜ (23,5%) ‰È¤ÎÔ„·Ó ÙËÓ ·ÁˆÁ‹. §¤ÍÂȘ ÎÏÂȉȿ: ÙÔÈÚ·Ì¿ÙË, ·ÓıÂÎÙÈΤ˜ ÛÙ· Ê¿Ú̷η ÂÈÏË„›Â˜, ·È‰È΋ ËÏÈΛ·.
™˘ÓÙÔÌÔÁڷʛ˜
AEº∞ÓÙÈÂÈÏËÙÈÎfi Ê¿ÚÌ·ÎÔ
AEDAnti-epileptic drug
KN™∫ÂÓÙÚÈÎfi Ó¢ÚÈÎfi Û‡ÛÙËÌ·
CBZ∫·Ú‚·Ì·˙›ÓË OXCOÍηڂ·˙›ÓË
PHTº·ÈÓ˘ÙÔ˝ÓË
VGBµÈÁη̷ÙÚ›ÓË LTG§·ÌÔÙÚÈÁ›ÓË
CLB∫ÏÔÌ·˙¿ÌË VPAµ·ÏÚÔ˚Îfi Ô͇ TGB∆È·Áη̛ÓË PBº·ÈÓÔ‚·Ú‚ÈÙ¿ÏË ETM∞ÈıÔÛÔ˘ÍÈÌ›‰Ë TPM∆ÔÈÚ·Ì¿ÙË CORT∫ÔÚÙÈÎÔÂȉ‹ CLZ∫ÏÔÓ·˙¿ÌË ACTH™˘ÓıÂÙÈ΋ ·‰ÚÂÓÔÎÔÚÙÈÎÔÙÚfiÔ˜ ÔÚÌfiÓË ∂ ∂ÈÏË„›· æ∫∂æ˘¯ÔÎÈÓËÙÈ΋ ÂͤÏÈÍË MRIª·ÁÓËÙÈ΋ ÙÔÌÔÁÚ·Ê›· ÂÁÎÂÊ¿ÏÔ˘
IVH∂Ó‰ÔÎÔÈÏȷ΋ ·ÈÌÔÚÚ·Á›·
GABA°¿Ì·-·ÌÈÓÔ-‚Ô˘Ù˘ÚÈÎfi Ô͇
∂ÈÛ·ÁˆÁ‹ ¶·Ú¿ ÙË ÛËÌ·ÓÙÈ΋ ÚfiÔ‰Ô ÛÙË ıÂڷ›· ÙˆÓ
ÂÈÏË„ÈÒÓ Ì ÙËÓ ÂÈÛ·ÁˆÁ‹ ÈηÓÔ‡
were observed in 10/17 patients (58.8%) and included weight loss and loss of appetite in 4, aggressiveness in 4, somnolence and difficulty in concentration in 2 patients. As a conclusion, topiramate was shown to be quite effective and safe as adjunctive therapy in 11/17 children and adolescents, with a wide range of cryptogenic and symptomatic resistant epilepsies. Response ≥50% was observed in 64.7% of the children in the study. The drug was generally well tolerated and the adverse effects of the drug that were found in 58.8% of the patients, were generally mild and transient. Four patients withdrew from treatment (23.5%).
Key words: topiramate, drug resistant epilepsies, childhood.
Ô‰ËÁÂ›Ù·È ÛÙËÓ ÔÏ˘Ê·Ú̷Λ· (1). ™ÙȘ ÂÚÈÙÒÛÂȘ ·˘Ù¤˜, Ë ÚfiÁÓˆÛË ·Ú·Ì¤ÓÂÈ ‰˘ÛÌÂÓ‹˜, ȉȷ›ÙÂÚ· fiÙ·Ó Ô
›‰ÈÔ˜ ·ÛıÂÓ‹˜ ·ÚÔ˘ÛÈ¿˙ÂÈ ÂÚÈÛÛfiÙÂÚÔ˘˜ ·fi ¤Ó·Ó ‹ ÔÚÈṲ̂ÓÔ˘˜ ȉȷ›ÙÂÚÔ˘˜ Ù‡Ô˘˜ ÎÚ›ÛÂˆÓ (.¯. ÙÔÓÈΤ˜ ‹ ·ÙÔÓÈΤ˜ ÎÚ›ÛÂȘ). ¶·ÚfiÌÔÈ·, Ë ·ÓıÂÎÙÈÎfiÙËÙ· ÛÙËÓ ·ÁˆÁ‹ Â›Ó·È Û˘Ó‹ı˘ ÁÈ· ÔÚÈṲ̂ӷ ÂÈÏËÙÈο Û‡Ó‰ÚÔÌ· (Û‡Ó‰ÚÔÌÔ Lennox-Gastaut, Û‡Ó‰ÚÔÌÔ West) ‹ ÂÍÂÏÈÎÙÈΤ˜ Ó¢ÚÔÏÔÁÈΤ˜ ·ı‹ÛÂȘ (.¯. ÚÔԉ¢ÙÈ΋ Ì˘ÔÎÏÔÓÈ΋ ÂÈÏË„›·), ·ÏÏ¿ Î·È ÁÈ· ÙȘ ÂÛÙȷΤ˜ ÎÚ›ÛÂȘ Ì ‹ ¯ˆÚ›˜ ‰Â˘ÙÂÚÔ·ı‹ ÁÂӛ΢ÛË (2,3). ™ÙÔ˘˜ ·ÛıÂÓ›˜ ·˘ÙÔ‡˜, Ì ٷ ·ÓˆÙ¤Úˆ ÂÈÏËÙÈο Û‡Ó‰ÚÔÌ· Î·È ÂÈÏË„›Â˜, ÔÈ Ó¢ÚÔ·ÎÙÈÓÔÏÔÁÈΤ˜ ÂÍÂÙ¿ÛÂȘ ÌÔÚ› Ó· ‰Â›ÍÔ˘Ó ‰È¿¯˘Ù˜ ÂÁÎÂÊ·ÏÈΤ˜ ‹ ÂÛÙȷΤ˜ ‚Ï¿‚˜ ÙÔ˘ ∫¡™, ÂÓÒ Û˘¯Ó¿ ·Ú·ÙËÚÔ‡ÓÙ·È ‰È·Ù·Ú·¯¤˜ Û˘ÌÂÚÈÊÔÚ¿˜, Ô˘ ÌÂÚÈΤ˜
ÊÔÚ¤˜ Û˘Óԉ‡ÔÓÙ·È Î·È ·fi ÓÔËÙÈ΋ ¤ÎÙˆÛË.
∏ ÙÔÈÚ·Ì¿ÙË Â›Ó·È ¤Ó· ∞∂º Ô˘ ¯ÚËÛÈÌÔÔÈÂ›Ù·È Û ÂÓ‹ÏÈΘ Î·È ·È‰È¿ ËÏÈΛ·˜ ≥2 ÂÙÒÓ, ˆ˜ Û˘ÌÏËڈ̷ÙÈ΋ ıÂڷ›· Û ÂÛÙÈ·ÎÔ‡˜ Û·ÛÌÔ‡˜, Ì ‹ ¯ˆÚ›˜ ‰Â˘ÙÂÚÔ·ı‹ ÁÂӛ΢ÛË, ηıÒ˜ Î·È Û ·ÛıÂÓ›˜ Ô˘ ‰ÂÓ Ú˘ıÌ›˙ÔÓÙ·È Ì ٷ ÎÏ·ÛÈο AEº (4,5). ¶ÚfiÛÊ·Ù˜ ÌÂϤÙ˜ ‰Â›¯ÓÔ˘Ó fiÙÈ ÙÔ Ê¿ÚÌ·ÎÔ ÌÔÚ› Ó· Â›Ó·È ¯Ú‹ÛÈÌÔ Î·È Û ÔÏÏÔ‡˜ ¿ÏÏÔ˘˜ Ù‡Ô˘˜ ÂÈÏËÙÈÎÒÓ ÎÚ›ÛÂˆÓ ‹ ÂÈÏËÙÈÎÒÓ Û˘Ó‰ÚfiÌˆÓ (ÁÂÓÈÎÂ˘Ì¤Ó˜ ÂÈÏË„›Â˜, ‚ÚÂÊÈÎÔ‡˜Û·ÛÌÔ‡˜, Û‡Ó‰ÚÔÌÔ Lennox-Gaustaut) (6-9).
ÂÙÒÓ (∞)¡ÔËÌÔÛ‡ÓË Ê˘ÛÈÔÏÔÁÈ΋™‡Ó‰ÚÔÌԌӷÚÍË 2 ÌËÓÒÓ: ˆ¯ÚfiÙËÙ·,‚ÔÏ‚ÔÛÙÚÔÊ‹,™‡ÓıÂÙË ÂÛÙȷ΋ ∂¶ÔÏ˘ÌÈÎÚÔÁ˘Ú›·
ÂÏÏÂÈÌÌ·ÙÈ΋˜ ÚÔÛÔ¯‹˜ ÙÒÛË ÎÂÊ·Ï‹˜,·ÒÏÂÈ· Û˘Ó›‰ËÛ˘,™˘Ìو̷ÙÈ΋ÈÓÈ·ÎÔ‡ ÏÔ‚Ô‡¢∂ Î·È ˘ÂÚÎÈÓËÙÈÎfiÙËÙ·˜Ïfi͢ÁÁ·˜ ∞fi ËÏÈΛ· 4 ÂÙÒÓ: Û‡ÓıÂÙ˜ ÂÛÙȷΤ˜ ÎÚ›ÛÂȘ 9 ÂÙÒÓ (∞)ª·ıËÛȷΤ˜ ‰È·Ù·Ú·¯¤˜ŒÓ·ÚÍË 3,5 ÂÙÒÓ: ¢∂ ÂÛÙÈ·Îfi status,™‡ÓıÂÙË ÂÛÙȷ΋ ∂™ÎÏ‹Ú˘ÓÛË·ÌÌˆÓ›Ô˘ Ì ‰Â˘ÙÂÚÔ·ı‹ ÁÂӛ΢ÛË™˘Ìو̷ÙÈ΋ΤڷÙÔ˜∞ƒ ŒÎÙÔÙÂ: Û‡ÓıÂÙ˜ ÂÛÙȷΤ˜ ÎÚ›ÛÂȘÎÚÔÙ·ÊÈÎÔ‡ÏÔ‚Ô‡ 12 ÂÙÒÓ (∞)¶ÚÔ‚Ï‹Ì·Ù· Û˘ÌÂÚÈÊÔÚ¿˜ Î·È ‹È· ŒÓ·ÚÍË: ÛÙÔ 1Ô 24ˆÚÔ ˙ˆ‹˜™‡ÓıÂÙË ÂÛÙȷ΋ ∂¶ÔÏ˘Î˘ÛÙÈ΋ ÓÔËÙÈ΋ ˘ÛÙ¤ÚËÛË™˘ÁÁÂÓ‹˜ ·Ú·-™Â ËÏÈΛ· 3 ÂÙÒÓ: statusÌ ‰Â˘ÙÂÚÔ·ı‹ÁÂӛ΢ÛËÂÁÎÂÊ·ÏÔÌ·Ï¿Î˘ÓÛË ÏËÁ›· Î·È ËÌÈÏËÁ›· ¢∂ ›ÎÙËÙË
Rubber Bleb Syndrome)ÂÛÙȷΤ˜ÎÚ›ÛÂȘ
·Ê·ÈÚ¤ÛÂȘ, drop attacksÂÚËÙÈ΋˜ ÂÁÎÂÊ·Ï›Ùȉ·˜)
(˙¿ÏË, ÛÈÂÏfiÚÚÔÈ·, ÙÒÛË
ÛÙfiÌ·ÙÔ˜, ‰˘Û·ÚıÚ›·, Û‡Á¯˘ÛË) 14 ÂÙÒÓ (∞)º˘ÛÈÔÏÔÁÈ΋ „˘¯ÔÎÈÓËÙÈ΋ ÂͤÏÈÍˌӷÚÍË 9 ÂÙÒÓ: ÙÔÓÈ΋ Û‡Û·ÛË Î·È
¿Óˆ ¿ÎÚÔ˘, ·Ê·ÈÚ¤ÛÂȘ, ÙÒÛË ÎÂÊ·Ï‹˜∫Ú˘ÙÔÁÂÓ‹˜ 14 ÂÙÒÓ (£)º˘ÛÈÔÏÔÁÈ΋ „˘¯ÔÎÈÓËÙÈ΋ ÂͤÏÈÍˌӷÚÍË 5 ÂÙÒÓ: ¤ÌÂÙÔÈ, ÔÛÌ‹, Êfi‚Ô˜,∂ÛÙȷ΋ ∂ ÌŸÁÎÔ˜ ∫¡™ ÁÂÓÈÎÂ˘Ì¤Ó˜ ÙÔÓÈÎÔÎÏÔÓÈΤ˜ ÎÚ›ÛÂȘ‰Â˘ÙÂÚÔ·ı‹ ÁÂӛ΢ÛË™˘Ìو̷ÙÈ΋
14 ÂÙÒÓ (∞)ª¤ÙÚÈ· ÓÔËÙÈ΋ ˘ÛÙ¤ÚËÛˌӷÚÍË 4 ÂÙÒÓ: Ïfi͢ÁÁ·˜, ¿ÓÔÈ·,™‡ÓıÂÙË ÂÛÙȷ΋ ∂§˘ÛÂÁÎÂÊ·Ï›·
∂ÁÎÂÊ·ÏÈ΋ ·Ú¿Ï˘ÛË
ÚÔۋψÛË ‚ϤÌÌ·ÙÔ˜ ηÈÌ ‰Â˘ÙÂÚÔ·ı‹ÁÂӛ΢ÛË (Û·ÛÙÈ΋ ÙÂÙÚ·¿ÚÂÛË)ÁÂÓÈÎÂ˘Ì¤Ó˜ ÙÔÓÈÎÔÎÏÔÓÈΤ˜ ÎÚ›ÛÂȘ™˘Ìو̷ÙÈ΋
19 ÂÙÒÓ (∞)º˘ÛÈÔÏÔÁÈ΋ „˘¯ÔÎÈÓËÙÈ΋ ÂͤÏÈÍˌӷÚÍË 12 ÂÙÒÓ: ÎÚ›ÛÂȘ Ì ·È̈‰›· ∂ÛÙȷ΋ ∂ ÌÂ∞ÚÙËÚÈÔÊÏ‚҉˘ ¢∂ Á·ÛÙÚÔÎÓËÌ›·˜, ÙÒÛË ÛÙÔ ¤‰·ÊÔ˜, ‰Â˘ÙÂÚÔ·ı‹ÁÂӛ΢ÛËÂÈÎÔÈÓˆÓ›· ∞ƒ ·ÒÏÂÈ· Û˘Ó›‰ËÛ˘, Ì˘ÔÎÏÔӛ˜, ·Ó‡„ˆÛË™˘Ìو̷ÙÈ΋ÌÂوȷ›Ô˘ ÏÔ‚Ô‡ ¯ÂÚÈÒÓ, ·Ê·›ÚÂÛË Ì ·fiÙÔÌÔ ‹¯Ô 14 ÂÙÒÓ (£)ª¤ÙÚÈ· ÓÔËÙÈ΋ ˘ÛÙ¤ÚËÛˌӷÚÍË 25 ÌËÓÒÓ-4 ÂÙÒÓ: ÂÛÙȷΤ˜™‡ÓıÂÙË ÂÛÙȷ΋ ∂º˘ÛÈÔÏÔÁÈ΋
10 ÂÙÒÓ (∞)™Ô‚·Ú‹ ÓÔËÙÈ΋ ˘ÛÙ¤ÚËÛË (·˘ÍË̤ӷ ŒÓ·ÚÍË 4 ÂÙÒÓ: Û‡ÓıÂÙ˜ÂÛÙȷΤ˜™‡ÓıÂÙË
ÁÂӛ΢ÛˉȷÊÚ¿ÁÌ·ÙÔ˜ -
ÔÚÁ·ÓÈο Ôͤ· Ô‡ÚˆÓ)Î·È ÁÂÓÈÎÂ˘Ì¤Ó˜ ÎÚ›ÛÂȘÌÂ
ÂÙÒÓ (£)™Ô‚·Ú‹ ÓÔËÙÈ΋ ˘ÛÙ¤ÚËÛË ŒÓ·ÚÍË 5 ÌËÓÒÓ-12 ÌËÓÒÓ:°ÂÓÈÎÂ˘Ì¤ÓË ∂º˘ÛÈÔÏÔÁÈ΋
(Û‡Ó‰ÚÔÌÔ Angelman)ÁÂÓÈÎÂ˘Ì¤Ó˜ ÙÔÓÈΤ˜ ÎÚ›ÛÂȘ Ì™˘Ìو̷ÙÈ΋
˘ÚÂÙfi Î·È status ∞fi 18 ÌËÓÒÓ: ÁÂÓÈÎÂ˘Ì¤Ó˜ ÙÔÓÈÎÔÎÏÔÓÈΤ˜
ÎÚ›ÛÂȘ, Ì˘ÔÎÏÔÓ›Â˜Î·È ·Ê·ÈÚ¤ÛÂȘ 10 ÂÙÒÓ (£)º˘ÛÈÔÏÔÁÈ΋ „˘¯ÔÎÈÓËÙÈ΋ ÂͤÏÈÍˌӷÚÍË 9 ÌËÓÒÓ-20 ÌËÓÒÓ:°ÂÓÈÎÂ˘Ì¤ÓË ∂º˘ÛÈÔÏÔÁÈ΋
ÔÏÏ·ÏÔ› ÂÈÏÂÁ̤ÓÔÈ ˘ÚÂÙÈÎÔ›∫Ú˘ÙÔÁÂÓ‹˜ Û·ÛÌÔ› Î·È status ™Â ËÏÈΛ· 7 ÂÙÒÓ: ÁÂÓÈÎÂ˘Ì¤Ó˜ ÙÔÓÈÎÔÎÏÔÓÈΤ˜ ÎÚ›ÛÂȘ 9 ÂÙÒÓ (∞)ª¤ÙÚÈ· ÓÔËÙÈ΋ ˘ÛÙ¤ÚËÛˌӷÚÍË 3 ÂÙÒÓ: ÁÂÓÈÎÂ˘Ì¤Ó˜ ÙÔÓÈΤ˜Î·ÈLennox-Gastaut ™˘ÁÁÂÓ‹˜ ÊÏÔÈÈ΋ ∏ÌÈÏËÁ›· ∞ƒ·ÙÔÓÈΤ˜ÎÚ›ÛÂȘ, ·Ê·ÈÚ¤ÛÂȘ Û‡Ó‰ÚÔÌÔ‰˘ÛÏ·Û›· ¢∂™˘Ìو̷ÙÈÎfi‚ÚÂÁÌ·ÙÈÎÔ‡ ÏÔ‚Ô‡ 6 ÂÙÒÓ (∞)™Ô‚·Ú‹
(Û·ÛÙÈ΋ ÙÂÙÚ·ÏËÁ›·)Û‡ÓıÂÙ˜ ÂÛÙȷΤ˜ ÎÚ›ÛÂȘ,Û‡Ó‰ÚÔÌÔÁÂÊ˘ÚÔ-·ÚÂÁÎÂÊ·ÏȉÈ΋ Ì˘ÔÎÏÔӛ˜, ·Ê·ÈÚ¤ÛÂȘ-
™˘Ìو̷ÙÈÎfi·ÙÚÔÊ›·
2. ∞ÔÙÂϤÛÌ·Ù· Ù˘ ·ÁˆÁ‹˜ Ì ∆PM
¶›Ó·Î·˜
Û‡Ó‰ÚÔÌÔ¶ÚÔËÁÔ‡ÌÂÓ·∞ÁˆÁ‹∞ÁˆÁ‹¶·ÚÂÓ¤ÚÁÂȘ¢fiÛˢȿÚÎÂÈ·ŒÎ‚·ÛË (º‡ÏÔ)Ê¿Ú̷ηÚÔ ∆PMÙÒÚ·(mg/kg/d)·Ú·Î/ıËÛ˘۷ÛÌÒÓ 6 ÂÙÒÓ (∞)™‡ÓıÂÙË ÂÛÙȷ΋ ∂VPA, CBZ,CBZ, LTG,CBZ, TPMŸ¯È910 Ì‹Ó˜>75% Ì›ˆÛË™˘Ìو̷ÙÈ΋VGB, LTGTGB
∏ÏÈΛ·∂
9 ÂÙÒÓ (∞)™‡ÓıÂÙË ÂÛÙȷ΋ ∂CBZ, VGBCBZ, VGBCBZ, TPMŸ¯È66 Ì‹Ó˜100%™˘Ìو̷ÙÈ΋ ·ÓÙ·fiÎÚÈÛË
12 ÂÙÒÓ (∞)™‡ÓıÂÙË ÂÛÙȷ΋ ∂ PB, VPA, LTG,VPA, CBZVP∞, CBZ, ∞ÓÔÚÂÍ›·, ÌÈÎÚ‹6,610 Ì‹Ó˜>50% Ì›ˆÛË Ì ‰Â˘ÙÂÚÔ·ı‹ ÁÂӛ΢ÛËTGB, OXC, CBZTPM·ÒÏÂÈ·‚¿ÚÔ˘˜™˘Ìو̷ÙÈ΋
13 ÂÙÒÓ (£)™‡ÓıÂÙË ÂÛÙȷ΋ ∂OXC, VPA,OXC, LTG,OXC, LTG,∞ÓÔÚÂÍ›·,ÌÈÎÚ‹515 Ì‹Ó˜>75% Ì›ˆÛË Ì ‰Â˘ÙÂÚÔ·ı‹ÁÂӛ΢ÛËLTG,CBZVPAVPA, TPM·ÒÏÂÈ·‚¿ÚÔ˘˜™˘Ìو̷ÙÈ΋ 11 ÂÙÒÓ (∞)∂ÛÙȷ΋ ∂PB, CBZ, VGB, CBZ, TGBCBZ, TPMŸ¯È89 Ì‹Ó˜100%∫Ú˘ÙÔÁÂÓ‹˜LTG, TGB ·ÓÙ·fiÎÚÈÛË
14 ÂÙÒÓ (∞)™‡ÓıÂÙË ÂÛÙȷ΋ ∂VPA, CBZ, TGB,VPA, PHT,VPA, PHTŸ¯È¢È·ÎÔ‹-∫·Ì›·∫Ú˘ÙÔÁÂÓ‹˜VGB, CLZ, OXCCBZ
14 ÂÙÒÓ (£)∂ÛÙȷ΋ ∂ Ì VPA, CBZ, OXC,CBZ, LTGCBZ, LTG™Ô‚·Ú‹ ˘ÓËÏ›·,¢È·ÎÔ‹-∫·Ì›· ‰Â˘ÙÂÚÔ·ı‹ÁÂӛ΢ÛËPHT, VGB, LTG‰È·Ù·Ú·¯¤˜·ÓÙ·fiÎÚÈÛË™˘Ìو̷ÙÈ΋
14 ÂÙÒÓ (∞)™‡ÓıÂÙË ÂÛÙȷ΋ ∂ VPA, CBZ,CBZCBZ, TPMŸ¯È56 Ì‹Ó˜>75% Ì›ˆÛË Ì ‰Â˘ÙÂÚÔ·ı‹ ÁÂӛ΢ÛËOXC™˘Ìو̷ÙÈ΋
19 ÂÙÒÓ (∞)∂ÛÙȷ΋ ∂ ÌÂVPA, CBZ, PHT,CBZ, VPACBZ, VPA, ∞ÒÏÂÈ·812 Ì‹Ó˜>75% Ì›ˆÛË ‰Â˘ÙÂÚÔ·ı‹ ÁÂӛ΢ÛËVGB, TGBTPM‚¿ÚÔ˘˜ >5 kg™˘Ìو̷ÙÈ΋
14 ÂÙÒÓ (£)™‡ÓıÂÙË ÂÛÙȷ΋ ∂PB, VPA, CBZ,PB, PHT,CBZ, PB, ÀÓËÏ›·109 Ì‹Ó˜>75% Ì›ˆÛË Ì ‰Â˘ÙÂÚÔ·ı‹ ÁÂӛ΢ÛËVGB, PHT,CLBCBZ, CLBTPM∫Ú˘ÙÔÁÂÓ‹˜ 10 ÂÙÒÓ (∞)™‡ÓıÂÙË ÂÛÙȷ΋ ∂CBZ, CLB, LTGCBZ, CLB,CBZ, CLB,58 Ì‹Ó˜<50% Ì›ˆÛË Ì ‰Â˘ÙÂÚÔ·ı‹ ÁÂӛ΢ÛËLTGTPM™˘Ìو̷ÙÈ΋ 14 ÂÙÒÓ (£)°ÂÓÈÎÂ˘Ì¤ÓË ∂PB, VPA, CLB, CBZ, CLZ, CBZ, CLZ,∂ÈıÂÙÈÎfiÙËÙ·,¢È·ÎÔ‹-∫·Ì›·™˘Ìو̷ÙÈ΋CBZ, CLZ, PHT, LTGLTG‰È·Ù·Ú·¯¤˜·ÓÙ·fiÎÚÈÛË
LTGÛ˘ÁΤÓÙÚˆÛ˘
·ÓÙ·fiÎÚÈÛË
10 ÂÙÒÓ (£)°ÂÓÈÎÂ˘Ì¤ÓË ∂PB, VPAVPAVPA, TPMŸ¯È35 Ì‹Ó˜100% -
∫Ú˘ÙÔÁÂÓ‹˜
9 ÂÙÒÓ (∞)Lennox-GastautVPA, CLB, ETM,VPA, CLB, VPA, TPM∞ÓÔÚÂÍ›·, ÌÈÎÚ‹515 Ì‹Ó˜100% Û‡Ó‰ÚÔÌÔLTG, LTG·ÒÏÂÈ·‚¿ÚÔ˘˜·ÓÙ·fiÎÚÈÛË™˘Ìو̷ÙÈÎfiSandoglobulin
6 ÂÙÒÓ (∞)Lennox-GastautVPA, CBZ, LTG,LTG, TGB,LTG, CLB∂Í·ÈÚÂÙÈ΋¢È·ÎÔ‹-∫·Ì›· Û‡Ó‰ÚÔÌÔVGB, CLB,CORT CLBÂÈıÂÙÈÎfiÙËÙ··ÓÙ·fiÎÚÈÛË∫Ú˘ÙÔÁÂÓ¤˜
6 ÂÙÒÓ (∞)Lennox-GastautVPA, CLB, LTGVPA, LTGVPA, LTG,∂ÈıÂÙÈÎfiÙËÙ·39 Ì‹Ó˜100% Û‡Ó‰ÚÔÌÔTPM·ÓÙ·fiÎÚÈÛË∫Ú˘ÙÔÁÂÓ¤˜
5 ÂÙÒÓ (£)µÚÂÊÈÎÔ› Û·ÛÌÔ› -VPA, PB, ACTH,VPA, PB,VPA, PB, ∞ÓÔÚÂÍ›·,109 Ì‹Ó˜<50% Lennox-GastautPHT, VGB, LTG,VGBVGB,TPM˘ÓËÏ›··ÓÙ·fiÎÚÈÛË Û‡Ó‰ÚÔÌÔCLZ™˘Ìو̷ÙÈÎfi
ÙÔÈÚ·Ì¿ÙË Î·Ù·Ù¿ÛÛÂÙ·È ¯ËÌÈο ÛÙÔ˘˜ ÛÔ˘ÏÊ·Ì·ÙÔ-ÌÔÓÔ۷ί·Ú›Ù˜ Î·È ‰Ú· ΢ڛˆ˜ ̤-
·Ó·ÛÙÔÏ‹˜ Ù˘ ÂͿψÛ˘ Ù˘ ÂÈÏËÙÈ΋˜ ÎÚ›Û˘, ·ÏÏ¿ Ù·˘Ùfi¯ÚÔÓ· ÌÔÚ› Ó· ·Ó‚¿˙ÂÈ Î·È ÙÔÓ ÂÈÏËÙÈÎfi Ô˘‰fi. Œ¯ÂÈ ÔÏÏ·Ïfi Ì˯·ÓÈÛÌfi
‰Ú¿Û˘ Î·È Ê·›ÓÂÙ·È fiÙÈ ·›˙ÂÈ Ú˘ıÌÈÛÙÈÎfi ÚfiÏÔ
ÛÙÔ˘˜ ÂÓÂÚÁÔÔÈË̤ÓÔ˘˜ ‰È·‡ÏÔ˘˜ Ó·ÙÚ›Ô˘ (·ÔÎÏ›ÂÈ ÙÔ˘˜ ‰È·‡ÏÔ˘˜ Ù˘ ÓÂ˘ÚˆÓÈ΋˜ ÌÂÌ‚Ú¿Ó˘), ÛÙÔ˘˜ ‰È·‡ÏÔ˘˜ ·Û‚ÂÛÙ›Ô˘, ÛÙÔ˘˜ GABA ˘Ô‰Ô¯Â›˜ (ÂÓÈÛ¯‡ÂÈ ÙË ‰Ú¿ÛË ÙÔ˘ GABA) Î·È ÛÙÔ˘˜ Kainate/AMPA ˘Ô‰Ô¯Â›˜ (·ÓÙ·ÁˆÓ›˙ÂÙ·È ÙÔ ÁÏÔ˘Ù·ÌÈÎfi Ô͇), Ì ·ÔÙ¤ÏÂÛÌ· ÙËÓ ·Ó·ÛÙÔÏ‹ Ù˘ ‰ÈÂÁÂÚÙÈ΋˜ Ó¢ÚÔÌÂÙ·‚›‚·Û˘ (10,11). ™ÙËÓ ·ÚÔ‡Û· ÌÂϤÙË Î·Ù·ÁÚ¿ÊÂÙ·È Ë ÂÌÂÈÚ›· Ù˘ Û˘ÁÎÂÎÚÈ̤Ó˘ ÎÏÈÓÈ΋˜ ·fi ÙË ¯Ú‹ÛË ÙÔ˘ Ê·ÚÌ¿ÎÔ˘, ˆ˜ Û˘ÌÏËڈ̷ÙÈ΋˜ ·ÁˆÁ‹˜, Û ·È-
‰È¿ Î·È ÂÊ‹‚Ô˘˜ Ì ̷ÎÚfi¯ÚÔÓË ·ÓıÂÎÙÈ΋ ÂÈÏË„›·. °›ÓÂÙ·È ·ÍÈÔÏfiÁËÛË Ù˘ ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙËÙ·˜
Ê·ÚÌ¿ÎÔ˘ ÛÙË Ú‡ıÌÈÛË ÙˆÓ ÎÚ›ÛˆÓ, ηıÒ˜ Î·È Ù˘ ·ÛÊ¿ÏÂÈ¿˜ ÙÔ˘ ÁÈ· ÙÔ˘˜ ÌÈÎÚÔ‡˜ ·ÛıÂÓ›˜.
Î·È Ì¤ıÔ‰ÔÈ
·È‰È¿ Î·È ¤ÊË‚ÔÈ ÌÂ
Î·È ·ÓıÂÎÙÈ΋ ÛÙ· Ê¿Ú̷η ÂÈÏË„›·, Ì ̤ÛË ‰È¿ÚÎÂÈ· ÓfiÛÔ˘ Ù· 6,9 ¤ÙË Î·È Û˘¯ÓfiÙËÙ· ÎÚ›ÛÂˆÓ ·fi 1 ‚‰ÔÌ·‰È·›ˆ˜ ¤ˆ˜ 20 ÎÚ›ÛÂȘ ËÌÂÚËÛ›ˆ˜. ™ÙË ÌÂϤÙË Û˘ÌÌÂÙ›¯·Ó Û˘ÓÔÏÈο 17 ·È‰È¿, 11 ·ÁfiÚÈ· Î·È 6 ÎÔÚ›ÙÛÈ·. ∏ ËÏÈΛ· ÙÔ˘˜ Î˘Ì·ÈÓfiÙ·Ó Û 4,5-19 ¤ÙË (̤ÛË ËÏÈΛ·: 10,4 ¤ÙË) Î·È ÔÈ ÎÚ›ÛÂȘ Û 5 ·È‰È¿ (30%) ›¯·Ó ¤Ó·ÚÍË ÛÙÔÓ ÚÒÙÔ ¯ÚfiÓÔ Ù˘ ˙ˆ‹˜. H ‰È¿ÁÓˆÛË ‚·Û›ÛÙËΠ۠ÎÏÈÓÈο, ËÏÂÎÙÚÔÂÁÎÂÊ·ÏÔÁÚ·ÊÈο Î·È Ó¢ÚÔ-·ÂÈÎÔÓÈÛÙÈο (MRI) ‰Â‰Ô̤ӷ. ∏ ηٿٷÍË ÙˆÓ ÂÈÏËÙÈÎÒÓ ÎÚ›ÛÂˆÓ Î·È ÂÈÏËÙÈÎÒÓ Û˘Ó‰ÚfiÌˆÓ ¤ÁÈÓ ۇÌʈӷ Ì ÙËÓ Ù·ÍÈÓfiÌËÛË Ù˘ ¢ÈÂıÓÔ‡˜ ŒÓˆÛ˘ ηٿ Ù˘ ∂ÈÏË„›·˜ (ILAE, 1989) (12). ™‡Ìʈӷ Ì ·˘Ù‹, 11/17 ·ÛıÂÓ›˜ (64,7% ÙÔ˘ Û˘ÓfiÏÔ˘) ›¯·Ó Û˘Ìو̷ÙÈ΋ ·ÈÙÈÔÏÔÁ›·, ‰ËÏ·‰‹ Ë ·ÈÙÈÔÏÔÁ›· Ù˘ ÓfiÛÔ˘ ‹Ù·Ó ÁÓˆÛÙ‹ Ì ÙË ‚Ô‹ıÂÈ· ÙÔ˘ ·ÂÈÎÔÓÈÛÙÈÎÔ‡ ÂϤÁ¯Ô˘ (˘‹Ú¯Â ˘ÔΛÌÂÓË ‰È¿¯˘ÙË ‹ ÂÛÙȷ΋ ‚Ï¿‚Ë ÙÔ˘ ∫¡™). ™Â Û˘Ó¿ÚÙËÛË Ì ÙËÓ ÂÓÙfiÈÛË Ù˘ ÓfiÛÔ˘, ÔÈ 11 ·ÛıÂÓ›˜ Ù˘ ÌÂϤÙ˘ ›¯·Ó ÂÛÙȷ΋ ÂÈÏË„›· (8 Û˘Ìو̷ÙÈ΋, 3 ÎÚ˘ÙÔÁÂÓ‹) Î·È ÔÈ ˘fiÏÔÈÔÈ 6 ÁÂÓÈÎÂ˘Ì¤ÓË ÂÈÏË„›· (3 Û˘Ìو̷ÙÈ΋, 3 ÎÚ˘ÙÔÁÂÓ‹). ∞Ó·ÊÔ-
ÚÈο, Ù¤ÏÔ˜, Ì ÙÔ Â›‰Ô˜ ÙˆÓ ÂÈÏËÙÈÎÒÓ ÎÚ›ÛˆÓ, ·fi ÙÔ˘˜ 11 ·ÛıÂÓ›˜ Ì ÂÛÙȷ΋ ÂÈÏË„›· ÔÈ 8 ÂÌÊ¿ÓÈ˙·Ó Û‡ÓıÂÙ˜
ÂÛÙȷΤ˜ ÎÚ›ÛÂȘ, ÔÈ 5 Î·È Ì ‰Â˘ÙÂÚÔ·ı‹ ÁÂӛ΢ÛË Î·È ÔÈ 3
ÂÛÙȷΤ˜ ÎÚ›ÛÂȘ, ÔÈ 2 Î·È Ì ‰Â˘ÙÂÚÔ·ı‹ ÁÂӛ΢ÛË, ›Û˘. ∞fi ÙÔ˘˜ 6 ·ÛıÂÓ›˜ Ì ÁÂÓÈÎÂ˘Ì¤ÓË ÂÈÏË„›·, 1 ÂÌÊ¿ÓÈ˙ ÁÂÓÈÎÂ˘Ì¤Ó˜ ÙÔÓÈÎÔÎÏÔÓÈΤ˜ ÎÚ›ÛÂȘ, 1 Ì˘ÔÎÏÔÓÈΤ˜ ·Ê·ÈÚ¤ÛÂȘ, 1 ‚ÚÂÊÈÎÔ‡˜ Û·ÛÌÔ‡˜ ·Ú¯Èο, Ô˘ ÛÙË Û˘Ó¤¯ÂÈ· ÂÍÂÏ›¯ıËηÓ
Û ۇӉÚÔÌÔ Lennox-Gastaut ηÈ, Ù¤ÏÔ˜, 3 ·ÛıÂÓ›˜ ›¯·Ó
Û‡Ó‰ÚÔÌÔ Lennox-Gastaut (ÎÚ›ÛÂȘ ÙÔÓÈΤ˜, ·ÙÔÓÈΤ˜, ¿Ù˘Â˜ ·Ê·ÈÚ¤ÛÂȘ Î·È Ì˘ÔÎÏÔӛ˜). ™˘ÓÔÏÈο ‰Â, 8/17 ·ÛıÂÓ›˜ ›¯·Ó
¿Óˆ ·fi ¤Ó·Ó Ù‡Ô ÎÚ›ÛˆÓ.
™ÙÔÓ ¶›Ó·Î· 1 ·Ó·ÁÚ¿ÊÔÓÙ·È ·Ó·Ï˘ÙÈο Ë ËÏÈΛ· ¤Ó·Ú͢ Î·È ÔÈ Ù‡ÔÈ ÙˆÓ ÎÚ›ÛˆÓ, Ô ·ÂÈÎÔÓÈÛÙÈÎfi˜ ¤ÏÂÁ¯Ô˜ Î·È 109
‰fiÛ˘ ÙÔ˘ Ê·ÚÌ¿ÎÔ˘. ∂Í·›ÚÂÛË ·ÔÙ¤ÏÂÛ·Ó 3
·ÛıÂÓ›˜ Ì ¤ÓÙÔÓ˜ ·ÚÂÓ¤ÚÁÂȘ ·fi ÙÔ ∫¡™
(ÂÈıÂÙÈÎfiÙËÙ· Î·È Î·Ù·ÛÙÔÏ‹), ÛÙÔ˘˜ ÔÔ›Ô˘˜ ‰ÈÂ-
ÎfiË ÙÔ Ê¿ÚÌ·ÎÔ, ·ÊÔ‡ ·Ô‰Â›¯ıËΠfiÙÈ ‹Ù·Ó ηÈ
·Ó·ÔÙÂÏÂÛÌ·ÙÈÎfi ÛÙË Ú‡ıÌÈÛË ÙˆÓ ÎÚ›ÛˆÓ. ™Â
¿ÏϘ ‰ÈϤ˜-Ù˘ÊϤ˜, ÂÏÂÁ¯fiÌÂÓ˜ Ì placebo ÌÂ-
ϤÙ˜, Û ·ÛıÂÓ›˜ Ô˘ ıÂڷ‡ÔÓÙ·Ó Ì ÙÔÈÚ·-
Ì¿ÙË, ÔÈ ·ÚÂÓ¤ÚÁÂȘ ·fi ÙÔ ∫¡™, fiˆ˜ Ë Û˘Ó·È-
ÛıËÌ·ÙÈ΋ ·ÛÙ¿ıÂÈ·, Ë ˘ÓËÏ›·, ÔÈ ‰˘ÛÎÔϛ˜ Û˘-
ÁΤÓÙÚˆÛ˘, ÚÔÛÔ¯‹˜ Î·È ÌÓ‹Ì˘ Î·È Ë ÎfiˆÛË, ·Ú·ÙËÚÔ‡ÓÙ·Ó Ôχ ÈÔ Û˘¯Ó¿ Û˘ÁÎÚÈÙÈο ÌÂ
·ÛıÂÓ›˜ Û ıÂڷ›· Ì placebo (4,9). ∞ÓÙ›ıÂÙ·, ÛÙȘ ›‰È˜ ÌÂϤÙ˜, Ë ÂÈıÂÙÈ΋ Û˘ÌÂÚÈÊÔÚ¿ ·-
Ú·ÙËÚ‹ıËÎÂ, ÛÙÔ ›‰ÈÔ ÂÚ›Ô˘ ÔÛÔÛÙfi, ÛÙÔ˘˜
·ÛıÂÓ›˜ Û ıÂڷ›· Ì placebo (7%) Î·È ÛÙÔ˘˜
·ÛıÂÓ›˜ Û ıÂڷ›· Ì ÙÔÈÚ·Ì¿ÙË (10%) (4). °Â-
ÓÈο, ¿ÓÙˆ˜, ÔÈ ÚÔ·Ó·ÊÂÚı›Û˜ ‰È·Ù·Ú·¯¤˜ ÙÔ˘
∫¡™, Ô˘ Û˘¯Ó¿ ·Ú·ÙËÚÔ‡ÓÙ·È Î·È Î·Ù¿ ÙË ¯ÔÚ‹-
ÁËÛË ·ÚÎÂÙÒÓ ¿ÏÏˆÓ ·ÓÙÈÂÈÏËÙÈÎÒÓ Ê·ÚÌ¿ÎˆÓ (2-3,11), Â›Ó·È ÔÈ ÈÔ Û˘¯Ó¿ ·Ú·ÙËÚÔ‡ÌÂÓ˜ ‰È·Ù·Ú·¯¤˜ ηٿ ÙË ¯ÔÚ‹ÁËÛË Ù˘ ÙÔÈÚ·Ì¿Ù˘ (5,11,13,14,16), ·ÏÏ¿ Ê·›ÓÂÙ·È Ó· ˘Ô¯ˆÚÔ‡Ó Â›Ù Ì ÙË Û˘Ó¤¯ÈÛË Ù˘ ıÂڷ›·˜, ›Ù Ì ÙËÓ ÂÏ¿ÙÙˆÛË Ù˘ ¯ÔÚËÁÔ‡ÌÂÓ˘ ‰fiÛ˘. ∂ÈÚfiÛıÂÙ·, ÎÚ›ÛÈÌË ÛÙËÓ Î·Ù‡ı˘ÓÛË ·˘Ù‹ Â›Ó·È Ë ·ÚÁ‹ ÙÈÙÏÔÔ›ËÛË ÙˆÓ ‰fiÛÂˆÓ ÙÔ˘ Ê·ÚÌ¿ÎÔ˘ (·‡ÍËÛË 1 mg/kg/24 h ·Ó¿ 2 ‚‰ÔÌ¿‰Â˜), Ô˘ ·ÊÂÓfi˜ ‚ÔËı¿ÂÈ ÛÙÔ Ó·
ÂÌÊ·Ó›˙ÔÓÙ·È ÏÈÁfiÙÂÚ˜ ·ÓÂÈı‡ÌËÙ˜ ÂÓ¤ÚÁÂȘ, ·ÊÂÙ¤ÚÔ˘ Û˘Ì‚¿ÏÏÂÈ Î·È ÛÙÔÓ ¤ÏÂÁ¯Ô ÙˆÓ ÎÚ›ÛˆÓ,
Ì ÙË ÌÈÎÚfiÙÂÚË ‰˘Ó·Ù‹ ‰fiÛË Ê·ÚÌ¿ÎÔ˘ (5,11,17).
°ÂÓÈο, ¿ÓÙˆ˜, Ë ÙÔÈÚ·Ì¿ÙË Ê·›ÓÂÙ·È Ó· ›ӷÈ
·ÛʷϤ˜ Ê¿ÚÌ·ÎÔ, ÙÔ ÔÔ›Ô ¯·Ú·ÎÙËÚ›˙ÂÙ·È ·fi
ÙËÓ ¤ÏÏÂÈ„Ë ÛËÌ·ÓÙÈÎÔ‡ ÎÈÓ‰‡ÓÔ˘ ÛÔ‚·ÚÒÓ ‹ ·ÂÈ-
ÏËÙÈÎÒÓ ÁÈ· ÙË ˙ˆ‹ ·ÚÂÓÂÚÁÂÈÒÓ (11).
™˘ÌÂÚ·ÛÌ·ÙÈο, Ë ÙÔÈÚ·Ì¿ÙË Ê¿ÓËΠӷ ‚ÂÏ-
ÙÈÒÓÂÈ ÙÔÓ ¤ÏÂÁ¯Ô ÙˆÓ ÎÚ›ÛÂˆÓ Û ‰È¿ÊÔÚ· ÂÈÏË-
ÙÈο Û‡Ó‰ÚÔÌ· ·È‰ÈÒÓ Î·È ÂÊ‹‚ˆÓ (·ÓıÂÎÙÈο ÛÂ
¿ÏÏ· ·ÓÙÈÂÈÏËÙÈο Ê¿Ú̷η), ¯ÔÚËÁÔ˘Ì¤ÓË Û·Ó
Û˘ÌÏËڈ̷ÙÈ΋ ·ÁˆÁ‹ Ì·˙› Ì ¿ÏÏ· ÎÏ·ÛÈο ηÈ
ÓÂfiÙÂÚ· ·ÓÙÈÂÈÏËÙÈο Ê¿Ú̷η. ¶·Ú·ÙËÚ‹ıËÎÂ
·ÓÙ·fiÎÚÈÛË Û ÔÛÔÛÙfi ≥50%, ÛÙÔ ÌÂÁ·Ï‡ÙÂÚÔ
̤ÚÔ˜ ÙˆÓ ·È‰ÈÒÓ (64,7%) Î·È È‰È·›ÙÂÚ· ÛÙ· ·È-
‰È¿ Ì ÔÔÈ·Û‰‹ÔÙ ÌÔÚÊ‹˜ Î·È ·ÈÙÈÔÏÔÁ›·˜
ÂÛÙȷ΋ ÂÈÏË„›·, ÂÓÒ Ôχ ÈηÓÔÔÈËÙÈ΋ ıˆÚ›-
Ù·È Î·È Ë ·ÓÙ·fiÎÚÈÛË Ô˘ ¤‰ÂÈÍ·Ó ÛÙÔ Ê¿ÚÌ·ÎÔ ÔÈ ·ÛıÂÓ›˜ Ì ۇӉÚÔÌÔ Lennox-Gastaut. ∆Ô Ê¿ÚÌ·-
ÎÔ ‹Ù·Ó ÁÂÓÈο ηÏÒ˜ ·ÓÂÎÙfi ·fi ÙÔ Û‡ÓÔÏÔ ÙˆÓ
·ÛıÂÓÒÓ Î·È ÔÈ ·ÚÂÓ¤ÚÁÂȘ Ô˘ ·ÚÔ˘ÛÈ¿ÛÙËηÓ
ÛÙÔ 58,8% ‹Ù·Ó ˆ˜ › ÙÔ Ï›ÛÙÔÓ ‹È˜ Î·È ·-
ÚÔ‰ÈΤ˜, ÂÓÒ ÌfiÓÔ 4 ·ÛıÂÓ›˜ (23,5%) ‰È¤ÎÔ„·Ó
ÙËÓ ·ÁˆÁ‹. £· Ú¤ÂÈ, fï˜, Ó· ÙÔÓÈÛÙ› fiÙÈ ÔÈ ·ÒÙÂÚ˜ ·ÓÂÈı‡ÌËÙ˜ ÂÓ¤ÚÁÂȘ Â›Ó·È ·ÎfiÌË ¿ÁÓˆÛÙ˜.
µÈ‚ÏÈÔÁÚ·Ê›·
1. Thomas P, Arzimanoglou A.∂ÈÏË„›Â˜. 2Ë ÂΉ. ·Ó¿‰. ÛÙ· ÂÏÏËÓÈο, ∂. ∂Ή. ¶·ÚÈÛÈ¿ÓÔ˘ ∞.∂.; 2002. ÛÂÏ. 254.
2. Marson AG, Kadir ZA, Chadwick DW. New antiepileptic drugs: a systematic review of their efficacy and tolerability. BMJ 1996;313:1169-1174.
3. Ferrie CD, Livingston JH. The new anti-epileptic drugs: a review. Eur J Pediatr Neurol 1997;1:139-147.
4. Elterman RD, Glauser TA, Wyllie E, Reife R, Wu SC, Pledger G. A double-blind, randomized trial of topiramate as adjunctive therapy for partial-onset seizures in children. ¡eurology 1999;52:1338-1344.
5. Uldall P, Buchholt JM. Clinical experiences with topiramate in children with intractable epilepsy. Eur J Pediatr Neurol 1999;3:105-111.
6. Wheless JW. Use of topiramate in childhood generalized seizure disorders. J Child Neurol 2000;15 (1 suppl):S7-13.
7. Glauser TA, Clark PO, Strawsburg R. A pilot study of topiramate in the treatment of infantile spasms. Epilepsia 1998;39:1324-1328.
8. Glauser TA, Levisohn PM, Ritter F, Sachdeo RC. Topiramate in Lennox-Gastaut syndome: open-label treatment of patients completing a randomized controlled trial. Topiramate YL Study Group. Epilepsia 2000;41 (1 Suppl):S86-90.
9. Sachdeo RC, Glauser TA, Ritter F, Reife R, Lim P, Pledger G. A double-blind, randomized trial of topiramate in LennoxGastaut syndrome. Topiramate YL Study Group. Neurology 1999;52:1882-1887.
10. Shank RP, Gardocki JF, Streeter AJ, Maryanoff BE. An overview of the preclinical aspects of topiramate: pharmacology, pharmacokinetics, and mechanism of action. Epilepsia 2000;41 (1 Suppl):S3-9.
11. Bourgeois BF. Pharmacokinetics and pharmacodynamics of topiramate. J Child Neurol 2000;15 (1 suppl):S27-30.
12. Commission on Classification and Terminology of the International League Against Epilepsy. Proposal for revised classification of epilepsies and epileptic syndromes. Epilepsia 1989;30:389-399.
13. ƒ›˙Ô˘ Ã, ∫fiÙÛ·Ï˘ Ã, ¶·Ú·ÛÎÂ˘Ô˘Ï¿ÎÔ˜ ∂, ª·˙›ÁÔ˘ ∂, °È·ÓÓ¤ÏË ª, ¶··‚·ÛÈÏ›Ԣ ∞. ∆ÔÈÚ·Ì¿ÙË ˆ˜ ÚfiÛıÂÙË ·ÁˆÁ‹ Û ·ÓıÂÎÙÈΤ˜ ÂÈÏË„›Â˜ ·È‰ÈÒÓ Î·È ÂÊ‹‚ˆÓ - ÂÌÂÈÚ›· ÂÓfi˜ ¤ÙÔ˘˜. 16Ô ¶·ÓÂÏÏ‹ÓÈÔ ™˘Ó¤‰ÚÈÔ ∂ÏÏ‹ÓˆÓ ¡Â˘ÚÔÏfiÁˆÓ. £ÂÛÛ·ÏÔÓ›ÎË; 1999, π·ÓÔ˘¿ÚÈÔ˜ 20-23, ∆ÔÌ.ÂÚ›Ï: 9-15.
14. Yeung S, Ferrie CD, Murdoch-Eaton DG, Livingston JH. Topiramate for drug-resistant epilepsies. Eur J Pediatr Neurol 2000;4:31-33.
15. Cross JH. Epilepsy: topiramate asmonotherapy in children. Eur J Pediatr Neurol2001;5:∞73.
16. Levisohn PM. Safety and tolerability of topiramate in children. J Child Neurol 2000;15 (1 Suppl):S22-26.
17. Shorvon SD. Safety of topiramate: adverse events and relationships to dosing. Epilepsia 1996;37 (2 Suppl):S18-22.
HÌÂÚÔÌËÓ›· ˘Ô‚ÔÏ‹˜: 13-09-2002
HÌÂÚÔÌËÓ›· ¤ÁÎÚÈÛ˘: 24-01-2003
¢È‡ı˘ÓÛË ·ÏÏËÏÔÁÚ·Ê›·˜: ªÂÚfiË ∆˙Ô‡ÊË
∆Ô̤·˜ ÀÁ›·˜ ÙÔ˘ ¶·È‰ÈÔ‡π·ÙÚÈ΋ ™¯ÔÏ‹, ¶·Ó/ÌÈÔ πˆ·ÓÓ›ÓˆÓ
∆.£. 1186, ∆.∫. 451 10, πˆ¿ÓÓÈÓ·
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ªÂȈ̤ÓË ‰Ú·ÛÙÈÎfiÙËÙ· Ù˘ ·ÎÂÙ˘Ï¯ÔÏÈÓÂÛÙÂÚ¿Û˘ ÙˆÓ ÂÚ˘ıÚÔ΢ÙÙ·ÚÈÎÒÓ
ÌÂÌ‚Ú·ÓÒÓ
Ê·ÈÓ˘ÏÎÂÙÔÓÔ˘ÚÈÎÒÓ ·ÛıÂÓÒÓ
∫. ∂. ™Ô‡ÏË1, °. ∞. ∫·Ú›Î·˜2, π. ∆˙·ÌÔ˘Ú¿ÓË1, ∂. ªÈ¯ÂϷοÎË1, ™. ∆۷ΛÚ˘3
Reduced acetylcholinesterase activity of erythrocyte membranes from patients with phenylketonuria ∫. ∏. Schulpis1, G. A. Karikas2, I. Tjamouranis1, H. Michelakakis1, S. Tsakiris3
¶ÂÚ›ÏË„Ë: ™ÎÔfi˜ Ù˘ ·ÚÔ‡Û·˜ ÂÚÁ·Û›·˜ ‹Ù·Ó: ·) Ë Ì¤ÙÚËÛË Ù˘ ‰Ú·ÛÙÈÎfiÙËÙ·˜ Ù˘ ·ÎÂÙ˘Ï¯ÔÏÈÓÂÛÙÂÚ¿Û˘ (∞Ã) ÛÙȘ ÂÚ˘ıÚÔ΢ÙÙ·ÚÈΤ˜ ÌÂÌ‚Ú¿Ó˜ ·ÛıÂÓÒÓ Ì ÎÏ·ÛÈ΋ Ê·ÈÓ˘ÏÎÂÙÔÓÔ˘Ú›· (PKU) Î·È Ì·ÚÙ‡ÚˆÓ Î·È Ë Û˘Û¯¤ÙÈÛ‹ Ù˘ Ì ٷ ›‰· ÙˆÓ ·ÌÈÓÔͤˆÓ Ê·ÈÓ˘Ï·Ï·Ó›ÓË (º·È), Ù˘ÚÔÛ›ÓË (∆˘Ú) Î·È ·Ï·Ó›ÓË (∞Ï·) ÛÙÔ Ï¿ÛÌ· ÙÔ˘˜, fiˆ˜ ›Û˘ Î·È Ù˘ ÓÙÔ·Ì›Ó˘ (¡ÙÔ), ‚) Ë ÌÂϤÙË ÙˆÓ in vitro ÂȉڿÛÂˆÓ Ù˘ º·È, ∞Ï· Î·È Ù˘ º·È+∞Ï· ÛÙË ‰Ú·ÛÙÈÎfiÙËÙ· ÙÔ˘ ÂÓ˙‡ÌÔ˘. ∏ ‰Ú·ÛÙÈÎfiÙËÙ· Ù˘ ∞à ÚÔÛ‰ÈÔÚ›ÛÙËΠʈÙÔÌÂÙÚÈο ÛÙȘ ÂÚ˘ıÚÔ΢ÙÙ·ÚÈΤ˜ ÌÂÌ‚Ú¿Ó˜ PKU ·ÛıÂÓÒÓ, ÔÈ ÔÔ›ÔÈ ·ÎÔÏÔ˘ıÔ‡Û·Ó ÛˆÛÙ¿ ÙË ‰›·ÈÙ¿ ÙÔ˘˜ (ÔÌ¿‰· ∞, ¡=12), Û 11 PKU ·ÛıÂÓ›˜ Ì ¯·Ï·Ú‹ ‰›·ÈÙ· (ÔÌ¿‰· µ) Î·È Û 23 ˘ÁÈ›˜ ·ÛıÂÓ›˜ ·ÓÙ›ÛÙÔȯ˘ ËÏÈΛ·˜. ∆· ·ÌÈÓÔͤ· ÚÔÛ‰ÈÔÚ›ÛÙËÎ·Ó Ì ·˘ÙfiÌ·ÙÔ ·Ó·Ï˘Ù‹ ·ÌÈÓÔͤˆÓ Î·È Ë ¡ÙÔ Ì HPLC. In vitro, AÏ· (1,8 mM) ‹ º·È (1,8 mM) ‹ Û˘Á¯ÚfiÓˆ˜ º·È (1,8 mM)+∞Ï· (1,8 mM) ÚÔÛÙ¤ıËÎ·Ó ÛÙÔ Ì›ÁÌ· ˆ¿Ûˆ˜ ÙˆÓ Ì·ÚÙ‡ÚˆÓ, ÙˆÓ ·ÛıÂÓÒÓ Ù˘ ÔÌ¿‰·˜ ∞, ÂÓÒ ÌfiÓÔ AÏ· ÚÔÛÙ¤ıËΠÛÙÔ Ì›ÁÌ· Ù˘ ÔÌ¿‰·˜ µ. ∏ ‰Ú·ÛÙÈÎfiÙËÙ· Ù˘ ∞à (1,19±0,05 ¢OD/min x mg protein), ÔÈ Û˘ÁÎÂÓÙÚÒÛÂȘ Ù˘ ∆˘Ú (0,83±0,30 mg/dl) Î·È Ù˘¡ÙÔ (56±18 Ìmol/l) ‹Ù·Ó ÛËÌ·ÓÙÈο ÌÂȈ̤Ó˜ (60%, p<0,001) ÛÙËÓ ÔÌ¿‰· µ Û˘ÁÎÚÈÓfiÌÂÓ˜ Ì ÙËÓ ÔÌ¿‰· ∞ (3,01±0,18 ¢OD/min x mg protein, 2,09±0,7 mg/dl, 137±29 Ìmol/l) Î·È Ì ÙÔ˘˜ Ì¿ÚÙ˘Ú˜ (3,13±0,16 ¢OD/min x mg protein, 2,13±0,80 mg/dl, 142±22 Ìmol/l, p<0,001). ∏ º·È
Û˘Û¯ÂÙÈ˙fiÙ·Ó ·ÚÓËÙÈο Ì ÙËÓ ∞Ã Î·È ıÂÙÈο Ì ÙËÓ
1 πÓÛÙÈÙÔ‡ÙÔ ÀÁ›·˜ ÙÔ˘ ¶·È‰ÈÔ‡, ¡ÔÛÔÎÔÌÂ›Ô ¶·›‰ˆÓ “∞Á›· ™ÔÊ›·”, ∞ı‹Ó·
2 ªÔÓ¿‰· ∂Ó‰ÔÊϤ‚ÈˆÓ ¢È·Ï˘Ì¿ÙˆÓ Î·È º·ÚÌ·ÎÔÎÈÓËÙÈ΋˜, ¡ÔÛÔÎÔÌÂ›Ô ¶·›‰ˆÓ “∞Á›· ™ÔÊ›·”, ∞ı‹Ó·
3 ∂ÚÁ·ÛÙ‹ÚÈÔ ¶ÂÈÚ·Ì·ÙÈ΋˜ º˘ÛÈÔÏÔÁ›·˜, π·ÙÚÈ΋ ™¯ÔÏ‹ ¶·ÓÂÈÛÙËÌ›Ô˘ ∞ıËÓÒÓ
Abstract: The aims of this study were: a)to evaluate acetylcholinesterase (AChE) activity in erythrocyte membranes from phenylketonuric (PKU) patients and controls, b) to correlate AChE activity with plasma levels of phenylalanine (Phe), tyrosine (Tyr), alanine (Ala) and dopamine (DA), and c) to determine the in vitro effects of Phe, Ala and Phe plus Ala on AChE activities. AChE activity was determined spectrophotometrically in erythrocyte membranes from 12 PKU children adhering to their diet (group A), from 11 PKU children on a “loose diet”(group B) and from 23 controls. Amino acids were evaluated with an analyser and DA by HPLC. Ala (1.8 mM) and/or Phe (1.8 mM) were added to the enzyme incubation medium from the controls, and Ala alone was added to that from group B. AChE activity (1.19±0.05 ¢OD/min x mg protein), Tyr (0.83±0.30 mg/dl) and DA (56±18 Ìmol/l) were lower by about 60% in group B than in group A (3.01±0.18 ¢OD/min x mg protein, 2.09±0.70 mg/dl, 137±29 Ìmol/l, respectively, p<0.001) and in the control group (3.13±0.16 ¢OD/min x mg protein, 2.13±0.80 mg/dl, 142±22 Ìmol/l, respectively, p<0.001). Phe was correlated negatively with AChE activity and positively with Tyr and DA. In the control group, Ala reversed the inhibition of AChE by Phe, whereas no effect was observed on the enzyme activity in the PKU patients. In conclusion,a) the determination of AChE in erythrocyte membranes from PKU patients may be a peripheral marker for
1 Institute of Child Health, “Agia Sophia”Children’s Hospital, Athens 2 Division of Intravenous Solutions and Pharmacokinetics, “Agia Sophia”Children’s Hospital, Athens
3 Laboratory of Experimental Physiology, University of Athens Medical School
Ì·ÚÙ‡ÚˆÓ.∞ÓÙ›ıÂÙ·,Ë ∞Ï· ‰ÂÓ Â›¯Â ηӤӷ ·ÔÙ¤-
ÏÂÛÌ· ÛÙËÓ ∞Ã ÙˆÓ PKU ·ÛıÂÓÒÓ. ™˘ÌÂÚ·ÛÌ·ÙÈ-
ο, ·) Ë Ì¤ÙÚËÛË ∞à ÛÙȘ ÂÚ˘ıÚÔ΢ÙÙ·ÚÈΤ˜ ÌÂÌ-
‚Ú¿Ó˜ ·ÛıÂÓÒÓ Ì PKU ı· ÌÔÚÔ‡Û ӷ ıˆÚË-
ı› ˆ˜ Ô˘ÛÈ҉˘ ‰Â›ÎÙ˘ Ù˘ ÙÔÍÈÎfiÙËÙ·˜ Ù˘ º·È
ÛÙÔ ∫¡™, ‚)Ù· ˘„ËÏ¿ ›‰· º·È ¤¯Ô˘Ó ˆ˜ ·Ô-
Ù¤ÏÂÛÌ· ÙË ÌÂȈ̤ÓË ÛÙ¿ıÌË Ù˘ ¡ÙÔ Î·È ÙÔ˘ ÚÔ-
‰ÚÔÌÈÎÔ‡ Ù˘ ·ÌÈÓÔͤԘ ∆˘Ú, fiˆ˜ ›Û˘ ÙËÓ
·Ó·ÛÙÔÏ‹ Ù˘ ∞à ÛÙÔ˘˜ PKU ·ÛıÂÓ›˜ Ì Èı·Ó‹ ·‡ÍËÛË Ù˘ Û˘ÁΤÓÙÚˆÛ˘ Ù˘ ·ÎÂÙ˘Ï¯ÔÏ›Ó˘.
§¤ÍÂȘ ÎÏÂȉȿ: Ê·ÈÓ˘Ï·Ï·Ó›ÓË, ·ÎÂÙ˘Ï¯ÔÏÈÓÂÛÙÂ-
Ú¿ÛË, ÓÙÔ·Ì›ÓË, ·Ï·Ó›ÓË.
∂ÈÛ·ÁˆÁ‹ ∏ Ê·ÈÓ˘ÏÎÂÙÔÓÔ˘Ú›· (PKU) Â›Ó·È ¤Ó· ÌÂÙ·‚ÔÏÈ-
Îfi ÓfiÛËÌ· Ô˘ ÎÏËÚÔÓÔÌÂ›Ù·È Ì ˘ÔÏÂÈfiÌÂÓÔ
ۈ̷ÙÈÎfi ÁfiÓÔ ÌÂ Û˘¯ÓfiÙËÙ· 1:15000 ÁÂÓÓ‹ÛÂȘ. ∏
‰È·Ù·Ú·¯‹ ·˘Ù‹ ÙÔ˘ ÌÂÙ·‚ÔÏÈÛÌÔ‡ ÙÔ˘ ·ÌÈÓÔͤԘ
Ê·ÈÓ˘Ï·Ï·Ó›ÓË (º·È) ÔÊ›ÏÂÙ·È ÛÙËÓ ·Ó¿ÚÎÂÈ·
ÙÔ˘ Ë·ÙÈÎÔ‡ ÂÓ˙‡ÌÔ˘ ˘‰ÚÔÍ˘Ï¿ÛË Ù˘ º·È, ÌÂ
ÙËÓ ·˘ÍË̤ÓË Û˘ÁΤÓÙÚˆÛË ÙÔ˘ ·ÌÈ-
ÓÔͤԘ Û fiÏ· Ù· ‚ÈÔÏÔÁÈο ˘ÁÚ¿. OÈ PKU ·ÛıÂÓ›˜
¯ˆÚ›˜ ıÂڷ›· ÂÌÊ·Ó›˙Ô˘Ó „˘¯ÔÎÈÓËÙÈ΋ ηı˘ÛÙ¤-
ÚËÛË, ‰È·Ù·Ú·¯¤˜ Û˘ÌÂÚÈÊÔÚ¿˜, Û·ÛÌÔ‡˜, ¤Î˙ÂÌ· Î.Ï. (1). ∆· ˘„ËÏ¿ ›‰· Ù˘ º·È (7-20 mg/dl ‹ 0,4-1,2 mª) Ô˘ ÂÌÊ·Ó›˙ÔÓÙ·È ÛÙÔ˘˜ ·ÛıÂÓ›˜ Â›Ó·È È‰È·›ÙÂÚ· ‚Ï·ÙÈο ηٿ ÙÔÓ ÚÒÙÔ ¯ÚfiÓÔ ˙ˆ‹˜. OÈ ‚Ï¿‚˜ ·˘Ù¤˜ ÚÔÏ·Ì‚¿ÓÔÓÙ·È Ì ÙË
ÛˆÛÙ‹ ‰È·ÈÙËÙÈ΋ Ú‡ıÌÈÛË (2-4). ¢˘ÛÙ˘¯Ò˜, ÔÏÏÔ›
·fi ÙÔ˘˜ PKU ·ÛıÂÓ›˜ ‰ÂÓ ·ÎÔÏÔ˘ıÔ‡Ó ·˘ÛÙËÚ¿
ÙËÓ ÂȉÈ΋ ‰›·ÈÙ¿ ÙÔ˘˜ (¯·Ï·Ú‹ ‰›·ÈÙ·), Ì ·ÔÙ¤-
ÏÂÛÌ· ÙËÓ ·˘ÍË̤ÓË Û˘ÁΤÓÙÚˆÛË Ù˘ º·È ÛÙÔ ·›-
Ì· ÙÔ˘˜ Î·È ÙË ¯·ÌËÏ‹ Ù˘ÚÔÛ›ÓË (∆˘Ú), Ë ÔÔ›· ›-
Ó·È ÚÔ‰ÚÔÌÈ΋ Ô˘Û›· ÙÔ˘ Ó¢Úԉȷ‚È‚·ÛÙ‹ ÓÙÔ·-
Ì›ÓË (¡ÙÔ) (1,5). ™˘ÓÂÒ˜, Ù· ·Ú·ÙËÚÔ‡ÌÂÓ· ¯·-
ÌËÏ¿ ›‰· Ù˘ ∆˘Ú ¤¯Ô˘Ó ˆ˜ ·ÔÙ¤ÏÂÛÌ· ÙË
ÌÂȈ̤ÓË ·Ú·ÁˆÁ‹ ·‰ÚÂÓÂÚÁÈÎÒÓ ·ÌÈÓÒÓ fiˆ˜ Ë ¡ÙÔ, Ë ÔÔ›· ÌÂÈÒÓÂÙ·È ÛËÌ·ÓÙÈο (5,6). ∂›Û˘, Ù· ˘„ËÏ¿ ›‰· Ù˘ º·È ‚Ú¤ıËΠfiÙÈ ÂȉÚÔ‡Ó Î·È Û ¿ÏÏÔ˘˜ Ì˯·ÓÈÛÌÔ‡˜ Ó¢ÚÈ΋˜ ‰ÈÂÁÂÚÛÈÌfiÙËÙ·˜ (1,3), ·ÍÔÓÈ΋˜ Û‡Ó‰ÂÛ˘, Û˘Ó·ÙÈ΋˜ ·ÎÔÏÔ˘ı›·˜ Î.Ï. (7).
™Â ÚÔËÁÔ‡ÌÂÓ˜ in vitro ÌÂϤÙ˜, ÔÈ ‰Ú·ÛÙÈÎfiÙËÙ˜ Ù˘ ·ÎÂÙ˘Ï¯ÔÏÈÓÂÛÙÂÚ¿Û˘ (∞Ã) Û ÔÌÔÁÂÓÔÔ›ËÌ· ÂÁÎÂÊ¿ÏÔ˘ ÔÓÙÈÎÔ‡, ·ÏÏ¿ Î·È ÙÔ˘ ηı·ÚÔ‡ ÂÓ˙‡ÌÔ˘ Ô˘ ÚÔ¤Ú¯ÂÙ·È ·fi ÙÔ ¯¤ÏÈ E. electricus, ‚Ú¤ıËΠfiÙÈ ÌÂÈÒÓÔÓÙ·È Î·Ù¿ 20% fiÙ·Ó
ˆ·ÛıÔ‡Ó ÛÂ Û˘ÁÎÂÓÙÚÒÛÂȘ º·È 7-20 mg/dl ‹ 0,4-1,2 mª, Û‡ÓËı˜ ‡ÚËÌ· ÛÙÔ ·›Ì· PKU ·ÛıÂÓÒÓ Ì ¯·Ï·Ú‹ ‰›·ÈÙ· ‹ ¯ˆÚ›˜ ‰È·ÈÙËÙÈ΋ ·ÁˆÁ‹.
∂›Û˘, Û ¿ÏÏË ÂÚÁ·Û›· (9), Ë ‰Ú·ÛÙÈÎfiÙËÙ· Ù˘
∞à ÛÙÔ ‰È¿ÊÚ·ÁÌ· ÔÓÙÈÎÔ‡ Ì ·ÚÔ˘Û›· ˘„ËÏÔ‡
the neurotoxic brain effects of Phe, b) the low levels ofDA and its precursor Tyr result from high Phe levels whichinhibit AChE in PKU patients, probably causing higher acetylcholine concentrations.
Key words: phenylalanine, acetylcholinesterase, dopamine, alanine.
ÂȤ‰Ô˘ º·È, ‚Ú¤ıËΠÌÂȈ̤ÓË Î·Ù¿ 20%. ™Â Ì›· ÚfiÛÊ·ÙË in vitro ÌÂϤÙË (10) ·Ú·ÙËÚ‹ıËΠfiÙÈ ÙÔ
L-·Ï·Ó›ÓË (∞Ï·) ıÂÙÈÎÔÔÈ› ‹ ÚÔÛٷهÂÈ
ÙËÓ ∞à ÂÁÎÂÊ¿ÏÔ˘ ÔÓÙÈÎÔ‡ ‹ ηı·ÚÔ‡ ÂÓ˙‡ÌÔ˘ ·fi ÙËÓ ·Ó·ÛÙ·ÏÙÈ΋ ‰Ú¿ÛË Ù˘ º·È. ∞ÎfiÌË, ·Ó·Ê¤ÚÂÙ·È
Ë ∞à ¤ÌÌÂÛ· ÂËÚ¿˙ÂÙ·È ·fi ÙË ¡ÙÔ (11), Ë
ÂÁΤʷÏÔ PKU
Ì ˘„ËÏ¿ ›‰· º·È ÛÙÔ ·›Ì· ÙÔ˘˜ (12).
ÚÔÊ·Ó¤˜ fiÙÈ Ô ·ÓıÚÒÈÓÔ˜ ÂÁΤʷÏÔ˜
Â›Ó·È ÚÔÛÈÙfi˜ Û ̛· ¿ÌÂÛË ·ÍÈÔÏfiÁËÛË Ù˘
Ù˘ ∞Ã. ™˘ÓÂÒ˜, Â›Ó·È ÂӉȷʤÚÔÓ
·Ó¢ÚÂıÔ‡Ó ÂÚÈÊÂÚÈÎÔ› ‰Â›ÎÙ˜, ÔÈ ÔÔ›ÔÈ ı· Â›Ó·È ·ÓÙÈÚÔÛˆÂ˘ÙÈÎÔ› ÙˆÓ ÂȉڿÛÂˆÓ Ù˘ º·È ÛÙÔ ¤Ó˙˘ÌÔ ÙÔ˘ ∫¡™. ™ÙËÓ ·ÚÔ‡Û· ÂÚÁ·Û›· ÌÂÙÚ‹ıËÎÂ Ë ‰Ú·ÛÙÈÎfiÙËÙ· Ù˘ ∞à Û ÂÚ˘ıÚÔ΢ÙÙ·ÚÈΤ˜ ÌÂÌ‚Ú¿Ó˜ PKU ·ÛıÂÓÒÓ Î·È Ì·ÚÙ‡ÚˆÓ ·ÓÙ›ÛÙÔȯ˘ ËÏÈΛ·˜, ¤ÁÈÓÂ Û˘Û¯¤ÙÈÛË Ù˘ ‰Ú·ÛÙÈÎfiÙËÙ·˜ ÙÔ˘ ÂÓ˙‡ÌÔ˘ Ì ٷ ›‰· ÙˆÓ ·ÌÈÓÔͤˆÓ º·È, ∆˘Ú, ∞Ï· Î·È ÙÔ˘ Ó¢Úԉȷ‚È‚·ÛÙ‹ ¡ÙÔ Î·È ÌÂÏÂÙ‹ıËΠin vitro ÙÔ ·ÔÙ¤ÏÂÛÌ· Ù˘ ›‰Ú·Û˘ ‰È·ÊfiÚˆÓ Û˘ÁÎÂÓÙÚÒÛÂˆÓ º·È, ∞Ï·, ∞Ï·+º·È ÛÙËÓ ∞à ÂÚ˘ıÚÔ΢ÙÙ·ÚÈÎÒÓ ÌÂÌ‚Ú·ÓÒÓ PKU ·ÛıÂÓÒÓ, ·ÏÏ¿ Î·È Ì·ÚÙ‡ÚˆÓ.
ÀÏÈÎfi Î·È Ì¤ıÔ‰ÔÈ ™ÙËÓ ·ÚÔ‡Û· ÌÂϤÙË ¤Ï·‚·Ó ̤ÚÔ˜ 23 PKU ·ÛıÂÓ›˜, ÔÈ
ÔÔ›ÔÈ ‰È·¯ˆÚ›ÛÙËÎ·Ó Û ‰‡Ô ÔÌ¿‰Â˜. ∏ ÔÌ¿‰· ∞ (N=12) ÂÚÈÂÏ¿Ì‚·Ó ·ÛıÂÓ›˜ Ì ̤ÛË ËÏÈΛ· Ù· 6,8±1,2 ¤ÙË, Ì ۯ‰fiÓ Ê˘ÛÈÔÏÔÁÈο ›‰· º·È ÛÙÔ ·›Ì· ÙÔ˘˜ (º·È 1,57±0,52 mg/dl ‹ 0,10±0,03 mª). ∏ ÔÌ¿‰· µ (¡=11) ÂÚÈÂÏ¿Ì‚·Ó ·ÛıÂÓ›˜ Ì ̤ÛË ËÏÈΛ· Ù· 7,2±2,0 ¤ÙË, Û ¯·Ï·Ú‹ ‰›·ÈÙ· (º·È 28,45±1,5 mg/dl ‹ 1,72±0,09 mª). ∂›ÎÔÛÈ ÙÚÂȘ (¡=23) ˘ÁÈ›˜ Ì¿ÚÙ˘Ú˜, ·ÓÙ›ÛÙÔȯ˘ ËÏÈΛ·˜, ›¯·Ó Ê˘ÛÈÔÏÔÁÈο ›‰· º·È (1,45±0,60 mg/dl ‹ 0,09±0,03 mª). ŸÏÔÈ ÔÈ PKU ·ÛıÂÓ›˜ ·Ú·ÎÔÏÔ˘ıÔ‡ÓÙ·È ÛÙÔ πÓÛÙÈÙÔ‡ÙÔ ÀÁ›·˜ ÙÔ˘ ¶·È‰ÈÔ‡. ªÂ ÙËÓ Â˘Î·ÈÚ›· Ù˘ ÂÙ‹ÛÈ·˜ ·ÍÈÔÏfiÁËÛ˘ ÙˆÓ ·ÛıÂÓÒÓ, Ï‹ÊıËΠ·›Ì· 5,0 ml Û ˷ÚÈÓÈṲ̂ÓË Û‡ÚÈÁÁ·, 3 ÒÚ˜ ÌÂÙ¿ ÙËÓ Â›Û΄‹ ÙÔ˘˜, ÒÛÙ ӷ ›¯·Ó ÂÁÎÏÈÌ·ÙÈÛÙ› ÛÙÔ ÂÚÈ‚¿ÏÏÔÓ. ›‰Ú·ÛË Ù˘ º·È ÛÙË ‰Ú·ÛÙÈÎfiÙËÙ· Ù˘ ∞ÃÙˆÓ
∂ÓÙfi˜ 2 ˆÚÒÓ ·fi ÙËÓ ·ÈÌÔÏË„›·, ÙÔ ·›Ì· Ê˘ÁÔÎÂÓÙÚ‹ıËΠ(2000 g ÁÈ· 30 min ÛÙÔ˘˜ 4ÔC). ∆o ›˙ËÌ· χıËΠ3-4 ÊÔÚ¤˜ Ì ڢıÌÈÛÙÈÎfi ‰È¿Ï˘Ì· (250 mª tris (hydroxymethyl) aminomethane - HCl (tris HCl), pH 7,4, 140 mM NaCl, 1 mM MgCl2, 10 mM ÁÏ˘Îfi˙Ë) ÌÂÙ¿ ·fi 3 Ê˘ÁÔÎÂÓÙÚ‹ÛÂȘ. ™ÙÔ ÂÚ˘ıÚÔ΢ÙÙ·ÚÈÎfi ›˙ËÌ· ÚÔÛÙ¤ıËΠ1
ml ÙÔ˘ ›‰ÈÔ˘ Ú˘ıÌÈÛÙÈÎÔ‡ ‰È·Ï‡Ì·ÙÔ˜ Î·È Ê˘Ï¿¯ÙËΠÛÙÔ˘˜
4ÔC ÁÈ· 24 ÒÚ˜ ÚÈÓ ÙËÓ ÚÔ·Ú·Û΢‹ ÙˆÓ ÂÚ˘ıÚÔ΢ÙÙ·ÚÈÎÒÓ ÌÂÌ‚Ú·ÓÒÓ Ì ÙȘ ÌÂıfi‰Ô˘˜ Ô˘ ÂÚÈÁÚ¿ÊÔÓÙ·È
·fi ÙÔ˘˜ Galbraith Î·È Watts (13) Î·È ∫amber Î·È Û˘Ó (14). ™ÙȘ ÂÚ˘ıÚÔ΢ÙÙ·ÚÈΤ˜ ÌÂÌ‚Ú¿Ó˜ ÌÂÙÚ‹ıËÎÂ Ë ÚˆÙ½ÓË, fiˆ˜ ÂÚÈÁÚ¿ÊÂÙ·È ·fi ÙÔ˘˜ Lowry Î·È Û˘Ó (15) Î·È Ê˘Ï¿¯ÙËÎ·Ó ÁÈ· 2 ‚‰ÔÌ¿‰Â˜ ÛÙÔ˘˜ -40oC. ∆· ˘ÔÏ›ÌÌ·Ù·
Ù˘ ·ÈÌÔÛÊ·ÈÚ›Ó˘ ÛÙȘ ÌÂÌ‚Ú¿Ó˜ ÌÂÙÚ‹ıËÎ·Ó Ì kit (527-
A Sigma Chemical Co, St. Louis, USA) Î·È Ë ÙÈÌ‹ Ù˘ ·Ê·ÈÚ¤ıËΠ·fi ÙËÓ ÔÏÈ΋ ÚˆÙ½ÓË.
∏ ‰Ú·ÛÙÈÎfiÙËÙ· Ù˘ ∞à ÛÙȘ ÂÚ˘ıÚÔ΢ÙÙ·ÚÈΤ˜ ÌÂÌ-
‚Ú¿Ó˜ ÙˆÓ Ì·ÚÙ‡ÚˆÓ ÌÂÙÚ‹ıËΠÚÈÓ ‹ ÌÂÙ¿ ÙËÓ in vitro
ÚÔÂÒ·ÛË ÁÈ· 1 ÒÚ· ÌÂ º·È 30 mg/dl (=1,8 mª) ‹ 1,8
mª ∞Ï· ‹ º·È+∞Ï·. ∆Ô ¤Ó˙˘ÌÔ Ô˘ ÚÔÂÚ¯fiÙ·Ó ·fi ÙȘ
ÌÂÌ‚Ú¿Ó˜ PKU ·ÛıÂÓÒÓ Ì ¯·Ï·Ú‹ ‰›·ÈÙ·, ÌÂÙÚ‹ıËΠÌÂ
ÙËÓ ·ÚÔ˘Û›· ‹ ÙËÓ ·Ô˘Û›· 1,8 mª ∞Ï·.
∏ ̤ÙÚËÛË Ù˘ ‰Ú·ÛÙÈÎfiÙËÙ·˜ Ù˘ ∞à ÛÙȘ ÂÚ˘ıÚÔ΢Ù-
Ù·ÚÈΤ˜ ÌÂÌ‚Ú¿Ó˜ PKU ·ÛıÂÓÒÓ Î·È Ì·ÚÙ‡ÚˆÓ Ú·ÁÌ·-
ÙÔÔÈ‹ıËΠ̠ÙË Ì¤ıÔ‰Ô Ellman Î·È Û˘Ó (16), fiˆ˜ ÙÚÔ-
ÔÔÈ‹ıËÎÂ ·fi ÙÔÓ Tsakiris (17).
OÈ ÔÛÔÙÈÎÔ› ÚÔÛ‰ÈÔÚÈÛÌÔ› ÙˆÓ ·ÌÈÓÔͤˆÓ º·È, ∆˘Ú ηÈ
∞Ï· ¤ÁÈÓ·Ó Ì ·˘ÙfiÌ·ÙÔ ·Ó·Ï˘Ù‹ ·ÌÈÓÔͤˆÓ (Biotronic LC 5001), ¯ÚËÛÈÌÔÔÈÒÓÙ·˜ ÙË ÓÔÚÏ¢ΛÓË ˆ˜ standard. ∆Ô CV (%) ÁÈ· ÙË º·È, ÙËÓ ∆˘Ú Î·È ÙËÓ ∞Ï· ‹Ù·Ó 3,1, 2,9 Î·È 2,8, ·ÓÙ›ÛÙÔȯ·. ∏ ¡ÙÔ ÌÂÙÚ‹ıËΠ̠∏PLC ÛÙÔ Ï¿ÛÌ· (11) ÌÂ
CV (%) 3,4.
∆· ·ÔÙÂϤÛÌ·Ù· ·Ó·Ï‡ıËÎ·Ó Ì ANOVA Î·È t-test. OÈ ‚·ıÌÔ› Û˘Û¯¤ÙÈÛ˘ ˘ÔÏÔÁ›ÛÙËÎ·Ó Ì ÙÔ Spearman test ÛÂ
∏/À, ¯ÚËÛÈÌÔÔÈÒÓÙ·˜ ÙÔ SPSS 10.0 ÛÙ·ÙÈÛÙÈÎfi ·Î¤ÙÔ.
∞ÔÙÂϤÛÌ·Ù·
Ÿˆ˜ ·ÚÔ˘ÛÈ¿˙ÂÙ·È ÛÙÔÓ ¶›Ó·Î· 1, ÔÈ Û˘ÁÎÂÓÙÚÒÛÂȘ Ù˘ ∆˘Ú, Ù˘ ¡ÙÔ Î·È Ë ‰Ú·ÛÙÈÎfiÙËÙ· Ù˘ ∞à ÛÙËÓ ÔÌ¿‰· µ ÙˆÓ PKU ·ÛıÂÓÒÓ ‹Ù·Ó ÛÙ·ÙÈÛÙÈ-
ο ÛËÌ·ÓÙÈο ¯·ÌËÏfiÙÂÚ˜ (ÂÚ›Ô˘ 60%, p<0,001), Û˘ÁÎÚÈÓfiÌÂÓ˜ Ì ÂΛӘ ÙˆÓ Ì·ÚÙ‡-
ÚˆÓ, fiˆ˜ ›Û˘ Î·È Ù˘ ÔÌ¿‰·˜ ∞. Ÿˆ˜ ‹Ù·Ó
·Ó·ÌÂÓfiÌÂÓÔ, Ù· ›‰· º·È ‹Ù·Ó ÛËÌ·ÓÙÈο ·˘ÍË̤ӷ ÛÙËÓ ÔÌ¿‰· µ, ÂÓÒ Ë ∞Ï· ‰ÂÓ ·ÚÔ˘Û›·ÛÂ
οÔÈ· ‰È·ÊÔÚ¿ Û fiϘ ÙȘ ÔÌ¿‰Â˜ ÌÂϤÙ˘.
™ÙÔÓ ¶›Ó·Î· 2 Ê·›ÓÂÙ·È fiÙÈ Ë ‰Ú·ÛÙÈÎfiÙËÙ· Ù˘
∞Ã Û˘Û¯ÂÙÈ˙fiÙ·Ó ¿ÌÂÛ· Ì ٷ ›‰· Ù˘ ¡ÙÔ Î·È
ÙÔ˘ ÚÔ‰ÚfiÌÔ˘ ·ÌÈÓÔͤԘ Ù˘ ∆˘Ú, ·ÏÏ¿ ‰ÂÓ Û˘Û¯ÂÙÈ˙fiÙ·Ó Ì ÙËÓ ∞Ï·. ∞ÓÙ›ıÂÙ·, Ë ‰Ú·ÛÙÈÎfiÙËÙ·
ÙÔ˘ ÂÓ˙‡ÌÔ˘ ¤‰ÂÈÍ ÈÛ¯˘Ú‹ ·ÚÓËÙÈ΋ Û˘Û¯¤ÙÈÛË ÌÂ
Ù· ›‰· Ù˘ º·È. ™ÙÔÓ ¶›Ó·Î· 3 ·ÚÔ˘ÛÈ¿˙ÔÓÙ·È Ù· in vitro ·Ô-
ÙÂϤÛÌ·Ù· Ù˘ ÚÔÂÒ·Û˘ ÙˆÓ ·ÌÈÓÔͤˆÓ º·È, ∞Ï· ‹ ∞Ï·+º·È ÛÙÔ ÌÂÌ‚Ú·ÓÈÎfi ¤Ó˙˘ÌÔ ∞à ÛÙȘ
ÂÚ˘ıÚÔ΢ÙÙ·ÚÈΤ˜ ÌÂÌ‚Ú¿Ó˜ ÙˆÓ Ì·ÚÙ‡ÚˆÓ.
ŸÙ·Ó ÚÔÛÙ¤ıËΠ∞Ï· (1,8 mM) ÛÙÔ Ì›ÁÌ· Ô˘
ÂÌÂÚÈ›¯Â ÙÔ ·Ó·ÛÙ·Ï̤ÓÔ ¤Ó˙˘ÌÔ ·fi ÙË º·È ÛÙȘ ÂÚ˘ıÚÔ΢ÙÙ·ÚÈΤ˜ ÌÂÌ‚Ú¿Ó˜ ÙˆÓ Ì·ÚÙ‡ÚˆÓ, Ë
‰Ú·ÛÙÈÎfiÙËÙ· ÙÔ˘ ÂÓ˙‡ÌÔ˘ ·ӋÏı ÛÙËÓ ·Ú¯È΋ ÙÈÌ‹. ∏ º·È ÛÂ Û˘ÁΤÓÙÚˆÛË 30 mg/dl (1,8 mM),
ÌÂÙÚ‹ıËΠÛÙÔ Ï¿ÛÌ· ÙˆÓ ·ÛıÂÓÒÓ Ù˘
ÔÌ¿‰·˜ µ, ·Ó¤ÛÙÂÈÏÂÙËÓ ∞Ãηٿ35% (p<0,001).
›‰È· Û˘ÁΤÓÙÚˆÛË Ù˘ ∞Ï·, fï˜, ‰ÂÓ Â¤ÊÂÚ Û ·˘Ù‹ ÙËÓ ÂÚ›ÙˆÛË Î·Ó¤Ó· ·ÔÙ¤ÏÂÛÌ· (p>0,05). ™˘˙‹ÙËÛË
∏ ›ÛÔ‰Ô˜ ÙˆÓ ·ÌÈÓÔͤˆÓ ‰È·Ì¤ÛÔ˘ ÙÔ˘ ·ÈÌ·ÙÔÂÁÎÂÊ·ÏÈÎÔ‡ ÊÚ·ÁÌÔ‡ ÂËÚ¿˙ÂÙ·È ·fi ÔÏÏÔ‡˜ ·Ú¿ÁÔÓÙ˜. π‰È·›ÙÂÚ·, Ë ÌÂÙ·ÊÔÚ¿ Ù˘ º·È Î·È Ù˘
∆˘Ú Á›ÓÂÙ·È ÛÙÔ ›‰ÈÔ Û‡ÛÙËÌ· ÌÂÙ·ÊÔÚ¿˜ (5). ª›· ÌÂÁ¿ÏË ·‡ÍËÛË Ù˘ Û˘ÁΤÓÙÚˆÛ˘ ÂÓfi˜ ·ÌÈÓÔͤԘ, fiˆ˜ Ù˘ º·È ÛÙËÓ ÔÌ¿‰· µ ÙˆÓ ·ÛıÂÓÒÓ, ·ÚÂÌÔ‰›˙ÂÈ ¿ÏÏ· ·ÌÈÓÔͤ·, fiˆ˜ ÙËÓ ∆˘Ú, Ó· ÂÈÛ¤ÏıÔ˘Ó ÛÙÔÓ ÂÁΤʷÏÔ (19). ªÂ ÙÔÓ ÙÚfiÔ ·˘Ùfi, Ù· ˘„ËÏ¿ ›‰· º·È ·ÚÂÌ‚·›ÓÔ˘Ó ÛÙË ÌÂÙ·ÙÚÔ‹ Ù˘ ∆˘Ú ÛÙÔÓ Ó¢Úԉȷ‚È‚·ÛÙ‹ ¡ÙÔ, Ô ÔÔ›Ô˜ ÂËÚ¿˙ÂÈ ÙË ‰Ú·ÛÙÈÎfiÙËÙ· Ù˘ ∞à (11). ∏ ·Ú·ÙËÚÔ‡ÌÂÓË ·fi ¿ÏÏÔ˘˜ ÂÚ¢ÓËÙ¤˜ (20) ·Ó·ÛÙÔÏ‹ Ù˘
¶›Ó·Î·˜ 1. ∂›Â‰· ÓÙÔ·Ì›Ó˘, ·ÌÈÓÔͤˆÓ Î·È ‰Ú·ÛÙÈÎfiÙËÙ·˜ ·ÎÂÙ˘Ï¯ÔÏÈÓÂÛÙÂÚ¿Û˘ (∞Ã) Û ʷÈÓ˘ÏÎÂÙÔÓÔ˘ÚÈÎÔ‡˜ ·ÛıÂÓ›˜ Î·È Ì¿ÚÙ˘Ú˜
OÌ¿‰· ∞OÌ¿‰· µª¿ÚÙ˘Ú˜ (¡=12)(¡=11)(¡=23)
º·È (mg/dl)1,57±0,52· 28,45±1,50‚ 1,45±0,60Á
∆˘Ú (mg/dl)2,09±0,70· 0,83±0,30‚ 2,13±0,80Á
AÏ· (mg/dl)4,07±0,60· 3,79±1,0‚ 3,85±1,00Á
¡ÙÔ (Ìmol/l)137±29· 56±18‚ 142±22Á
AX (¢OD/min x mg protein)3,01±0,18· 1,19±0,05‚ 3,13±0,16Á
OÈ ÙÈ̤˜ ÂÎÊÚ¿˙ÔÓÙ·È: ª¤ÛË ÙÈÌ‹±ÛÙ·ıÂÚ‹ ·fiÎÏÈÛË
º·È, ∆˘Ú, ¡ÙÔ, AX: ·/‚, ‚/Á=p<0,001 Î·È ·/Á=M™
∞Ï·: ·/‚, ·/Á, ‚/Á=ª™
ª™: ªË ÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈ΋ ÙÈÌ‹
(¡=11)
º·È∆˘Ú∞Ï·¡ÙÔ
∞Ã-0,58**+0,44*+0,12+0,46*
* p<0,05
** p<0,01
¡a+, K+-ATP¿Û˘ ÛÙȘ ÂÚ˘ıÚÔ΢ÙÙ·ÚÈΤ˜ ÌÂÌ‚Ú¿-
Ó˜ PKU ·ÛıÂÓÒÓ ı· ÌÔÚÔ‡ÛÂ, ›Û˘, Ó· ·Ô-
‰Ôı› ÛÙ· ¯·ÌËÏ¿ ›‰· Ù˘ ¡ÙÔ (¶›Ó·Î·˜ 1) (21,22) Î·È ÛÙ· ˘„ËÏ¿ ›‰· ·ÎÂÙ˘Ï¯ÔÏ›Ó˘ (23).
∂›Û˘, Ù· ›‰· Ù˘ ·ÎÂÙ˘Ï¯ÔÏ›Ó˘ ı· ÌÔÚÔ‡-
Û·Ó Ó· ·˘ÍËıÔ‡Ó ÛÙÔ Ï¿ÛÌ· PKU ·ÛıÂÓÒÓ, fiˆ˜
›Û˘ ÛÙÔÓ ÔÏÈÎfi ÂÁΤʷÏÔ, ÛÙÔ ‰È¿ÊÚ·ÁÌ· Ô-
ÓÙÈÎÔ‡ (8,9) Î·È ÛÂ Û˘ÁÎÂÎÚÈ̤Ó˜ ÂÚÈÔ¯¤˜ ÙÔ˘
ÂÁÎÂÊ¿ÏÔ˘ ÔÓÙÈÎÔ‡ (ÚfiÛıÈÔ˜ ÏÔ‚fi˜, Èfiη-
ÌÔ˜) (24), ˆ˜ ·ÔÙ¤ÏÂÛÌ· Ù˘ ·Ó·ÛÙÔÏ‹˜ Ù˘ ∞Ã
·fi ÙË º·È (8,9,24). ∫·Ù¿ Û˘Ó¤ÂÈ·, Ë ‰Ú·ÛÙÈÎfiÙËÙ· ÙÔ˘ ÂÓ˙‡ÌÔ˘ Na+, K+-ATP¿ÛË ı· ÌÔÚÔ‡ÛÂ, ›-
Û˘, Ó· ÌÂȈı› (9,20,24). O Weil-Maiherbe (25)
‚ڋΠÌÂȈ̤ӷ Ù· ›‰· Ù˘ ¡ÙÔ ÛÙÔ Ï¿ÛÌ·
PKU ·ÛıÂÓÒÓ ¯ˆÚ›˜ ıÂڷ›·. ∆· Â˘Ú‹Ì·Ù· ·˘Ù¿
Û˘ÌʈÓÔ‡Ó Ì ÂΛӷ ÙˆÓ PKU ·ÛıÂÓÒÓ Ù˘ ·-
ÚÔ‡Û·˜ ÌÂϤÙ˘ Ì ¯·Ï·Ú‹ ‰›·ÈÙ· (ÔÌ¿‰· µ).
ŒÙÛÈ, ı· ÌÔÚÔ‡Û·Ì ӷ ˘Ôı¤ÛÔ˘Ì fiÙÈ ·ÓÙÈÚÔ-
ÛˆÂ‡Ô˘Ó ÂΛӷ ÙÔ˘ ∂¡À (5,12).
¶·Ú·ÙËÚ‹ıËΠÌÂÁ¿ÏË Ì›ˆÛË (60%) Ù˘ ‰Ú·-
ÛÙÈÎfiÙËÙ·˜ Ù˘ ∞à ÛÙȘ ÂÚ˘ıÚÔ΢ÙÙ·ÚÈΤ˜ ÌÂÌ‚Ú¿-
Ó˜ ÙˆÓ PKU ·ÛıÂÓÒÓ Ù˘ ÔÌ¿‰·˜ µ, Û˘ÁÎÚÈÓfiÌÂ-
ÓË Ì ÂΛÓË Ô˘ ÌÂÙÚ‹ıËΠin vitro (20%) ÛÙÔÓ
ÂÁΤʷÏÔ Î·È ÛÙÔ ‰È¿ÊÚ·ÁÌ· ÔÓÙÈÎÔ‡, fiˆ˜ ›-
Û˘ ÛÙÔ Î·ı·Úfi ¤Ó˙˘ÌÔ (8,9), ·ÚÔ˘Û›· ˘„ËÏÒÓ
ÂȤ‰ˆÓ º·È. ™˘ÓÂÒ˜, Ë ÌÂÁ¿ÏË ·Ó·ÛÙÔÏ‹ Ù˘
∞à ÛÙ· ÂÚ˘ıÚÔ·ÙÙ·Ú· ÙˆÓ ·ÛıÂÓÒÓ Ì·˜ ı· ÌÔ-
ÚÔ‡Û ӷ ·Ô‰Ôı› ÛÙËÓ Â› Ì·ÎÚfi ¯ÚfiÓÔ Â›‰Ú·-
ÛË Ù˘ º·È ÛÙË ÌÂÌ‚Ú¿ÓË ÙÔ˘ ÂÓ˙‡ÌÔ˘. ™Â Ì›· Úfi-
ÛÊ·ÙË ÂÚÁ·Û›· (10) ‰È·ÈÛÙÒıËΠfiÙÈ Ë ∞Ï· ÚÔÊ˘Ï¿ÛÛÂÈ ÙËÓ in vitro ·Ó·ÛÙÔÏ‹ Ù˘ ∞à ·fi ÙË º·È, ·ÓÙ·ÁˆÓÈ˙fiÌÂÓË ÙÔ ·ÚˆÌ·ÙÈÎfi ·˘Ùfi ·ÌÈÓÔ͇ ÙfiÛÔ
ÛÙÔÓ ÂÁΤʷÏÔ ÔÓÙÈÎÔ‡, fiÛÔ Î·È ÛÙÔ Î·ı·Úfi ¤Ó˙˘ÌÔ. ¶Ú¿ÁÌ·ÙÈ, ÛÙËÓ ·ÚÔ‡Û· ÂÚÁ·Û›·, Ë ∞Ï·
ÚÔÛÙÈı¤ÌÂÓË ÛÙÔ Ì›ÁÌ· ÚÔÂÒ·Û˘ Ù˘ ∞Ã, ÛÙÔ ÔÔ›Ô ÚÔ¸‹Ú¯Â º·È, ÚÔʇϷÍ ÙÔ ¤Ó˙˘ÌÔ
ÙˆÓ ÂÚ˘ıÚÔ΢ÙÙ·ÚÈÎÒÓ ÌÂÌ‚Ú·ÓÒÓ ÙˆÓ Ì·ÚÙ‡ÚˆÓ ·fi ÙËÓ ·Ó·ÛÙ·ÏÙÈ΋ ‰Ú¿ÛË ÙÔ˘. ∞ÓÙ›ıÂÙ·, Ë ∞Ï· ‰ÂÓ Î·ÙfiÚıˆÛ ӷ ·ÓÙÈÛÙÚ¤„ÂÈ ÛÙÔ Ê˘ÛÈÔÏÔÁÈÎfi ÙËÓ ·Ó·ÛÙ·Ï̤ÓË ∞Ã ÙˆÓ ÂÚ˘ıÚÔ΢ÙÙ·ÚÈÎÒÓ ÌÂÌ‚Ú·ÓÒÓ
¶›Ó·Î·˜ 3. ¢Ú·ÛÙÈÎfiÙËÙ· Ù˘ ∞à Û ÂÚ˘ıÚÔ΢ÙÙ·ÚÈΤ˜ ÌÂÌ‚Ú¿Ó˜ Ì·ÚÙ‡ÚˆÓ ÌÂÙ¿ ·fi in vitro ÂÒ·ÛË Ì º·È, ∞Ï· Î·È º·È+∞Ï·
™˘ÁΤÓÙÚˆÛËAX ‰Ú·ÛÙÈÎfiÙËÙ· (mM)(¢OD/min x mg protein)
ª¿ÚÙ˘Ú˜03,03±0,13 º·È1,81,90±0,14*** ∞Ï·1,82,96±0,21 º·È+∞Ï·1,83,10±0,19
*** p<0,001
OÈ ÙÈ̤˜ ÂÎÊÚ¿˙ÔÓÙ·È: ª¤ÛË ÙÈÌ‹±ÛÙ·ıÂÚ‹ ·fiÎÏÈÛË
Ì·ÎÚfi ¯ÚfiÓÔ Â›‰Ú·ÛË ÙˆÓ ·˘ÍËÌ¤ÓˆÓ ÂȤ‰ˆÓ Ù˘ º·È ÛÙȘ ÂÚ˘ıÚÔ΢ÙÙ·ÚÈΤ˜ ÌÂÌ‚Ú¿Ó˜ ÙˆÓ PKU ·ÛıÂÓÒÓ, ÂӉ¯Ô̤ӈ˜ ¤¯ÂÈ ˆ˜ ·ÔÙ¤ÏÂÛÌ· ÙË Ì›ˆÛË ÙˆÓ ÂÓÂÚÁÒÓ ÂÓ˙˘ÌÈÎÒÓ ÌÔÚ›ˆÓ ÛÙË ÌÂÌ‚Ú¿ÓË. ∆Ô ÁÂÁÔÓfi˜ ·˘Ùfi ı· ÌÔÚÔ‡Û ӷ ·Ô‰Ôı› ÛÙË Ì›ˆÛË Ù˘ ÚˆÙÂ˚ÓÈ΋˜ Û‡ÓıÂÛ˘, Ô˘ ÚÔ¤Ú¯ÂÙ·È ·fi Ù· ˘„ËÏ¿ ›‰· Ù˘ º·È (26-28). ∫·ı’ fiÛÔÓ Â›Ó·È ÁÓˆÛÙfi fiÙÈ ÔÈ ‰ÈÂÚÁ·Û›Â˜ Ù˘ ÌÓ‹Ì˘ Û˘Û¯ÂÙ›˙ÔÓÙ·È Ì ¯ÔÏÈÓÂÚÁÈÎÔ‡˜ Î·È ·‰ÚÂÓÂÚÁÈÎÔ‡˜ Ì˯·ÓÈÛÌÔ‡˜ (29), fiˆ˜ ›Û˘ fiÙÈ Ë ¯·ÌËÏ‹ ‰Ú·ÛÙÈÎfiÙËÙ· Ù˘ ∞Ã Û˘Û¯ÂÙ›˙ÂÙ·È ÛÙÂÓ¿ ÌÂ
ÌÂȈ̤ӷ ›‰· Ù˘ ¡ÙÔ Û‡Ìʈӷ Ì ÙËÓ ·ÚÔ‡Û· ÌÂϤÙË, ı· ÌÔÚÔ‡Û ӷ ˘ÔÛÙËÚȯı›
ÌÔÚÔ‡Ó Û οÔÈÔ
ÙȘ ‚Ï¿‚˜ ÙˆÓ PKU ·ÛıÂÓÒÓ. ∞ÎfiÌË, ı· ÌÔÚÔ‡Û ӷ ÂÚÌËÓ¢ı› Î·È Ô ·Ú·ÙËÚÔ‡ÌÂÓÔ˜ ÙÚfiÌÔ˜ ÛÙÔ˘˜ PKU ·ÛıÂÓ›˜ ¯ˆÚ›˜ ıÂڷ›·, ÏfiÁˆ ·‡ÍËÛ˘ Ù˘ Û˘ÁΤÓÙÚˆÛ˘ Ù˘ ·ÎÂÙ˘Ï¯ÔÏ›Ó˘, ˆ˜ ·ÔÙ¤ÏÂÛÌ· Ù˘ ÌÂȈ̤Ó˘ ‰Ú·ÛÙÈÎfiÙËÙ·˜ Ù˘ ∞Ã.
∂˘¯·ÚÈÛٛ˜
OÈ Û˘ÁÁÚ·Ê›˜ ıˆÚÔ‡Ó ˘Ô¯Ú¤ˆÛ‹ ÙÔ˘˜ Ó· ¢¯·ÚÈÛÙ‹ÛÔ˘Ó ÙËÓ Î·. ∆·ÛÛÔÔ‡ÏÔ˘ ∫·ÏÏÈfiË ÁÈ· ÙËÓ ÂÈÌÂÏË̤ÓË ‰·ÎÙ˘ÏÔÁÚ¿ÊËÛË Ù˘ ÂÚÁ·Û›·˜.
µÈ‚ÏÈÔÁÚ·Ê›·
1. Scriver C, Kaufman S, Eisensmith R, Woo S. The hyperphenylalaninemias. In: Scriver C, Beadet A, Sly W, Valle D, editors. The metabolic and molecular bases of inherited disease. New York, NY: McGraw Hill; 1995. p. 1015-1075.
2. Missiou-Tsagaraki S, Soulpi K, Loumakou M. Phenylketonuria in Greece: 12 years experience. J Ment Defic Res 1988;32:271-281.
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Ë Â›
4. Francis D. Diets for sick children. 4th ed. Oxford: Blackwell Scientific Publ; 1989. p. 224-255.
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15. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem 1951;193:265-275.
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17. Tsakiris S. Effects of L-phenylalanine on acetylcholinesterase and Na+, K+-ATPase activities in adult and aged rat brain. Mech Ageing Dev 2001;122:491-501.
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20. Bedin M, Estrella CH, Ponzi D, Duarte DV, Dutra-Filho CS, Wyse AT et al. Reduced Na+, K+-ATPase activity in erythrocyte membranes from patients with phenylketonuria. Pediatr Res 2001;50:56-60.
21. Bogdanski DF, Tissari A, Brodie BB. Role of sodium, potassium, ouabain and reserpine in uptake, storage and metabolism of biogenic amines in synaptosomes. Life Sci 1968;7:419-428.
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HÌÂÚÔÌËÓ›· ˘Ô‚ÔÏ‹˜: 18-06-2002
HÌÂÚÔÌËÓ›· ¤ÁÎÚÈÛ˘: 17-01-2003
¢È‡ı˘ÓÛË ·ÏÏËÏÔÁÚ·Ê›·˜:∫ÏÂÔ¿ÙÚ· ™Ô‡ÏË
πÓÛÙÈÙÔ‡ÙÔ ÀÁ›·˜ ÙÔ˘ ¶·È‰ÈÔ‡, ¡ÔÛÔÎÔÌÂ›Ô ¶·›‰ˆÓ “∞Á›· ™ÔÊ›·”, ∆.∫. 115 27, ∞ı‹Ó·
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∫ÏÈÓÈ΋ Î·È ‚ÈÔ¯ËÌÈ΋ ÚÔÛ¤ÁÁÈÛË
°. ª·ÚfiÔ˘ÏÔ˜1, ¶. ∞˘ÁÔ˘ÛÙ›‰Ô˘ - ™·‚‚ÔÔ‡ÏÔ˘2, ∫. µÔ‡‰Ú˘3, ∫. ™Ô‡ÏË4, ™. ª¿ÛÙÔÚ·1, ∂. ¢ÚÔÁοÚË5
Organic acidurias in Greece - 6 years’ experience. Clinical and biochemical approach G. Maropoulos1, P. Augoustides - Savvopoulou2, K. Voudris3, K. Soulpi4, S. Mastora1, E. Drogari5
¶ÂÚ›ÏË„Ë: ∆· ÙÂÏÂ˘Ù·›· ¯ÚfiÓÈ·, ÛÙËÓ ∂ÏÏ¿‰·, Ë
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ÛÌ·ÙÔÁÚ·Ê›·˜ Ì·˙ÒÓ (MS) Î·È Ù˘ ·¤ÚÈ·˜ ¯ÚˆÌ·-
ÙÔÁÚ·Ê›·˜ (GC) ÛÙÔÓ ÚÔÛ‰ÈÔÚÈÛÌfi ÙˆÓ ÔÚÁ·ÓÈ-
ÎÒÓ ÔͤˆÓ ·ÔηχÙÂÈ ÙÔÓ Ù‡Ô Ù˘ ÔÚÁ·ÓÈ΋˜
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∞fi ÙȘ ·Ó·Ï‡ÛÂȘ ‰È·ÈÛÙÒıËΠ۠85 ·ÛıÂÓ›˜
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1
∆Ì‹Ì·, ¡ÔÛÔÎÔÌÂ›Ô ¶·›‰ˆÓ “¶. & ∞. ∫˘ÚÈ·ÎÔ‡”, ∞ı‹Ó·
2 µÈÔ¯ËÌÈÎfi ∂ÚÁ·ÛÙ‹ÚÈÔ ∞’ ¶·È‰È·ÙÚÈ΋˜ ∫ÏÈÓÈ΋˜ ∞¶£, °¶¡ πÔÎÚ¿ÙÂÈÔ, £ÂÛÛ·ÏÔÓ›ÎË
3 ¡Â˘ÚÔÏÔÁÈÎfi ∆Ì‹Ì·, ¡ÔÛÔÎÔÌÂ›Ô ¶·›‰ˆÓ “¶. & ∞. ∫˘ÚÈ·ÎÔ‡”, ∞ı‹Ó·
4 πÓÛÙÈÙÔ‡ÙÔ ÀÁ›·˜ ÙÔ˘ ¶·È‰ÈÔ‡, ¡ÔÛÔÎÔÌÂ›Ô ¶·›‰ˆÓ “∞Á. ™ÔÊ›·”, ∞ı‹Ó·
5 ∞’ ¶·È‰È·ÙÚÈ΋ ∫ÏÈÓÈ΋ ¶·ÓÂÈÛÙËÌ›Ô˘ ∞ıËÓÒÓ, ¡ÔÛÔÎÔÌÂ›Ô ¶·›‰ˆÓ “∞Á. ™ÔÊ›·”, ∞ı‹Ó·
Abstract: Selective screening for inherited defects of organic acid metabolism is a continuously expanding diagnostic procedure in Greece. The diagnosis of the organic acidurias, a high incidence group of inborn errors of metabolism (IEM), is based primarily on identification of the organic acid profile in the urine and/or acylcarnitine profile abnormalities in the blood using gas chromatography-mass spectrometry (GC-MS) and tandem mass spectrometry respectively. The in time diagnosis of the majority of these disorders is critical for early initiation of effective treatment and improved prognosis. The last six years, urine and blood specimens of 5021 patients at high risk for IEM, in particular defects of organic acid metabolism, were investigated in the Clinical Biochemistry Laboratory of the “P. & A. Kyriakou” Children’s Hospital. IEM were diagnosed in 85 patients, specifically, MMA (8), propionic acidemia (3), glutaric aciduria type I (6), SSADH (6), L-2hydroxy-glutaric aciduria (4), Canavan disease (2), HMGlyase deficiency (2), ‚-ketothiolase deficiency (1), EPEMA syndrome (1), MADD (1), MCAD deficiency (7) and 5 cases with dicarboxylic aciduria and abnormal acylcarnitine profile analyses. Thirteen patients presented with toxic hyperammonemia (6 cases of OTC, 1 of ASS, 4 of LPI and 2 with persistent mild orotic aciduria), 10
1 Department of Biochemistry, “P. & A. Kyriakou”Children’s Hospital, Athens
2 Biochemistry Laboratory, 1st Pediatric Clinic of Aristotelion University, Ippokration Hospital, Thessaloniki
3 Department of Neurology, “P. & A. Kyriakou”Children’s Hospital, Athens
4 Institute of Child Health, “Ag. Sophia”Children’s Hospital, Athens
5 1st Pediatric Clinic of Athens University, “Ag. Sophia”Children’s Hospital, Athens
˘ÂÚ·Ì̈ÓÈ·ÈÌ›· Î·È ÔÚÔÙÈ΋ Ô͢Ԣڛ·, Ù·˘ÙÔÔÈ-
‹ıËΠÂÓ˙˘ÌÈ΋ ·Ó¿ÚÎÂÈ· ÙÔ˘ ·ÎÏÔ˘ Ù˘ Ô˘Ú›·˜ Î·È Ï˘ÛÈÓÔ˘ÚÈ΋ ‰˘Û·ÓÂÍ›· ÛÙËÓ ÚˆÙ½ÓË (4 ·ÛıÂÓ›˜). ∞ÌÈÓÔ-ÔÍ˘Ô¿ıÂÈ· (·ÏηÙÔÓÔ˘Ú›·, ÓfiÛÔ˜ Ì ÔÛÌ‹ Ô‡ÚˆÓ Û·Ó ·fi ÛÈÚfiÈ ÛÊÂÓ‰¿ÌÔ˘, Ù˘ÚÔÛÈÓ·ÈÌ›· Ù‡Ô˘ π) ›¯·Ó 10 ·ÛıÂÓ›˜. O ·ÚÈıÌfi˜ ·˘ÙÒÓ ÙˆÓ ÌÂÙ·‚ÔÏÈÎÒÓ ‰È·Ù·Ú·¯ÒÓ, Ô ÔÔ›Ô˜ ·ÓÙÈÛÙÔȯ› Û ·ıÚÔÈÛÙÈ΋ Û˘¯ÓfiÙËÙ· 1:8696 ÁÂÓÓ‹ÛÂȘ Ù˘ Û˘ÁÎÂÎÚÈ̤Ó˘ ÂÚÈfi‰Ô˘ ÛÙË ¯ÒÚ·, ·ÔÙÂÏ› ¤Ó·Ó ÚÒÙÔ ‰Â›ÎÙË Ù˘ ¤ÎÊÚ·Û‹˜ ÙÔ˘˜ ÛÙÔÓ ÂÏÏËÓÈÎfi ÏËı˘ÛÌfi. ∂ÈϤÔÓ, Ô ÂÚÁ·ÛÙËÚÈ·Îfi˜ ¤ÏÂÁ¯Ô˜ Ô˘ Ú·ÁÌ·ÙÔÔÈ‹ıËÎÂ Û˘Ó¤‚·Ï ÛÙË ‰ÈÂÚ‡-
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¿ÚÎÂȘ ÚˆÙÔ·ıÔ‡˜ Á·Ï·ÎÙÈ΋˜ ÌÂÙ·‚ÔÏÈ΋˜
ÔͤˆÛ˘ (·Ó¿ÚÎÂȘ Û˘ÌÏÂÁÌ¿ÙˆÓ ·Ó·Ó¢ÛÙÈ΋˜ ·Ï‡ÛÔ˘ Û 9 ·ÛıÂÓ›˜ Î·È ·Ó¿ÚÎÂÈ· ˘ÚÔÛÙ·Ê˘ÏÈ΋˜ ‰Â¸‰ÚÔÁÂÓ¿Û˘ Û 4 ·ÛıÂÓ›˜). ∞ÎfiÌË, Û 247 ·ÛıÂÓ›˜ (5,3% ÙˆÓ ·Ó·Ï‡ÛˆÓ), ÛÙÔ Ê¿ÛÌ· ÙˆÓ ÔÚÁ·ÓÈÎÒÓ ÔͤˆÓ ‰È·ÈÛÙÒıËÎ·Ó ÂÓ‰ÂÈÎÙÈΤ˜ Î·È fi¯È ‰È·ÁÓˆÛÙÈΤ˜ ‰È·Ù·Ú·¯¤˜. ™ÙË ÌÂϤÙË ·Ú¤¯ÔÓÙ·È ÎÏÈÓÈΤ˜ ÏËÚÔÊÔڛ˜ ÛÙÔ 70% ÙˆÓ ·ÛıÂÓÒÓ Ô˘ ÂÍÂÙ¿ÛıËηÓ. ∆Ô 63,3% ÙˆÓ ·ÛıÂÓÒÓ ·ÚÔ˘Û›·Û ‰È·Ù·Ú·¯¤˜ ÙÔ˘ Ó¢ÚÈÎÔ‡ Û˘ÛÙ‹Ì·ÙÔ˜. OÈ ÂÚÈÛÛfiÙÂÚÔÈ ÂÍ ·˘ÙÒÓ Â›¯·Ó ¯·Ú·ÎÙËÚÈÛÙÈο ¯ÚfiÓÈ·˜ ÂÁÎÂÊ·ÏÔ¿ıÂÈ·˜. ™˘Ìو̷ÙÔÏÔÁ›· ÔÍ›·˜ ÂÁÎÂÊ·ÏÔ¿ıÂÈ·˜ ·ÚÔ˘Û›·Û ÙÔ 4,3% ÙˆÓ ·ÛıÂÓÒÓ. ¢È·Ù·Ú·¯¤˜ ۈ̷ÙÈ΋˜ ·Ó¿Ù˘Í˘ ·ÚÔ˘Û›·˙ ÙÔ 8,7% Î·È ÂȉÈΤ˜ ۈ̷ÙÈΤ˜ ÔÚÁ·ÓÈΤ˜ ‚Ï¿‚˜ ÙÔ 26,4%. ∆· ·Ú·¿Óˆ Â˘Ú‹Ì·Ù· Û¯ÔÏÈ¿˙ÔÓÙ·È ·fi ÎÏÈÓÈ΋ Î·È ‚ÈÔ¯ËÌÈ΋ ÛÎÔÈ¿, Ì ÛÙfi¯Ô ÙË ‚ÂÏÙ›ˆÛË Ù˘ ‰È¿ÁÓˆÛ˘ ·ÛıÂÓÒÓ Ì ÎÏËÚÔÓÔÌÈΤ˜ ÔÚÁ·ÓÈΤ˜ ÔÍ˘Ô˘Ú›Â˜ ÛÙËÓ ∂ÏÏ¿‰·.
§¤ÍÂȘ ÎÏÂȉȿ: ÂÓ‰ÔÁÂÓ‹ ÌÂÙ·‚ÔÏÈο ÓÔÛ‹Ì·Ù·, ÔÚÁ·ÓÈΤ˜ ÔÍ˘Ô˘Ú›Â˜, ·¤ÚÈ· ¯ÚˆÌ·ÙÔÁÚ·Ê›·-Ê·ÛÌ·ÙÔÁÚ·Ê›· Ì·˙ÒÓ.
∂ÈÛ·ÁˆÁ‹
patients had an amino acid disorder, namely, alkaptonuria (5), MSUD (3), tyrosinemia type I (2), and one patient had a pyrimidine disorder (DPD deficiency). These diagnoses indicate that the cumulative incidence of these disorders in Greece could be greater than 1:8696 births. In addition, 14 patients with primary lactic metabolic acidosis were identified and one with abnormalities of purine metabolism. Evaluation of the data shows a rather low diagnostic rate (about 1.67% of the patients studied). In addition to the specific diagnoses, significant urine organic acid abnormalities were found in 247 cases, with no defined cause. The main clinical symptoms of the patients examined were neurological disturbances, accounting for 63.3% of patients, the majority of which presented with indicative findings of chronic encephalopathy, and 4.3% with acute encephalopathy.Developmental delay and dysmorphic features were present in the 8.7% of the patients and organ failure in 26.4%. The clinical and laboratory findings of this study are presented with a view to increasing the awareness of the practicing pediatrician and improving healthcare planning in Greece to ensure effective diagnosis.
Key words: inborn errors of metabolism, organic acidurias, metabolic decompensation, gas chromatography-mass spectrometry.
∆· ÎÏËÚÔÓÔÌÈο ÌÂÙ·‚ÔÏÈο ÓÔÛ‹Ì·Ù· (∫ª¡Inherited metabolic disorders) ·ÔÙÂÏÔ‡Ó ÌÂÁ¿ÏË Î·È ‰È·ÚÎÒ˜ ·˘Í·ÓfiÌÂÓË ÔÌ¿‰· ÓÔÛËÌ¿ÙˆÓ ÌÂ Û˘¯Ó¿ ÛÔ‚·Ú¤˜ ÎÏÈÓÈΤ˜ ÂΉËÏÒÛÂȘ ÛÙË ÓÂÔÁÓÈ΋, ‚ÚÂÊÈ΋ Î·È ·È‰È΋ ËÏÈΛ· (1). ∞ÚÎÂÙ¿ ·fi ·˘Ù¿ ·ÔÙÂÏÔ‡Ó ÛËÌ·ÓÙÈÎfi ·›ÙÈÔ ÚfiÎÏËÛ˘ ÓÔÛËÚfiÙËÙ·˜ Î·È ıÓËÙfiÙËÙ·˜, ȉȷ›ÙÂÚ· ÛÙÔÓ ·È‰ÈÎfi ÏËı˘ÛÌfi (2). ŸÌˆ˜, Ë ¤ÁηÈÚË ‰È·ÁÓˆÛÙÈ΋ ‰ÈÂÚ‡ÓËÛ‹ ÙÔ˘˜ ÂÈÙÚ¤ÂÈ ÙËÓ ÂÊ·ÚÌÔÁ‹ Û˘¯Ó¿ ·ÔÙÂÏÂÛÌ·ÙÈ΋˜ ıÂڷ¢ÙÈ΋ ·ÁˆÁ‹˜ Î·È ÚÔÁÂÓÓËÙÈÎÔ‡ ÂϤÁ¯Ô˘. ™ÙËÓ ÔÌ¿‰· ÙˆÓ ∫ª¡ ÂÚÈÏ·Ì‚¿ÓÔÓÙ·È ¿Óˆ ·fi 469 ÓÔÛ‹Ì·Ù· Î·È Û‡Ìʈӷ Ì ÙËÓ Â˘Úˆ·˚΋ Ù·ÍÈÓfiÌËÛË ÙˆÓ ÓÔÛËÌ¿ÙˆÓ ·Ó‹ÎÔ˘Ó ÛÙËÓ Î·ÙËÁÔÚ›· ÙˆÓ Û¿ÓÈˆÓ ÓÔÛËÌ¿ÙˆÓ (rare disorders or orphan diseases) (3). ¶·Ú’ fiÏ· ·˘Ù¿, Ë ·ıÚÔÈÛÙÈ΋ Û˘¯ÓfiÙËÙ¿ ÙÔ˘˜ ÛÙÔÓ ÁÂÓÈÎfi ÏËı˘ÛÌfi, Û‡Ìʈӷ Ì ‰È¿ÊÔÚ˜ ÌÂϤÙ˜, Â›Ó·È ÌÂٷ͇ 1:600-2000 ÁÂÓÓ‹ÛÂȘ ˙ÒÓÙˆÓ ÓÂÔÁÓÒÓ (3-5). OÈ ÎÏÈÓÈΤ˜ ÂΉËÏÒÛÂȘ ÙÔ˘˜ ÔÊ›ÏÔÓÙ·È Û ÂÓ‰ÔÁÂÓ›˜ ‰È·Ù·Ú·¯¤˜
ÙˆÓ ÌÂÙ·‚ÔÏÈÎÒÓ ÏÂÈÙÔ˘ÚÁÈÒÓ (inborn errors of metabolism), ÔÈ Ôԛ˜ ÚÔηÏÔ‡ÓÙ·È ·fi Û˘ÁÎÂÎÚÈ̤Ó˜ ÂÓ˙˘ÌÈΤ˜ ·Ó¿ÚÎÂȘ ‹ ·fi ÙË Û‡ÓıÂÛË ÂÏ·Ùو̷ÙÈ΋˜ ‰ÔÌ‹˜ Î·È ÏÂÈÙÔ˘ÚÁ›·˜ ÚˆÙÂ˚ÓÒÓ (6). ∞›ÙÈÔ ·˘ÙÒÓ ÙˆÓ ·Ó·ÚÎÂÈÒÓ Â›Ó·È Û˘ÁÎÂÎÚÈ̤Ó˜ ÌÔÓÔÁÔÓȉȷΤ˜ ÌÂÙ·ÏÏ¿ÍÂȘ (Mendelian
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¶ÚÔ‚Ï‹Ì·Ù· ÔÌÈÏ›·˜67∞Ó·Ó¢ÛÙÈÎfi51 ¢È·Ù·Ú·¯¤˜ Û˘ÌÂÚÈÊÔÚ¿˜/·˘ÙÈÛÌfi˜67/46=113ª˘ÔηډÈÔ¿ıÂÈ·/ηډȷΤ˜ ·ÓˆÌ·Ï›Â˜56/24=80 ¡ÔËÙÈ΋ ηı˘ÛÙ¤ÚËÛË93∞ÈÌÔÔÈËÙÈÎfi62 ª·ÎÚÔÎÂÊ·Ï›·72∂Ó‰ÔÎÚÈÓÔÏÔÁÈÎfi25 ªÈÎÚÔÎÂÊ·Ï›·45¡ÂÊÚ¿70 À‰ÚÔΤʷÏÔ˜24¶ÂÙÈÎfi/ÏÔÈÌÒÍÂȘ206 ∂ÁÎÂÊ·ÏÈ΋ ·Ú¿Ï˘ÛË126¢¤ÚÌ·/ÙÚ›¯Â˜24 ∞Ù·Í›·/‰˘ÛÙÔÓ›·128/18=146ŸÚ·ÛË61 ÀÂÚÙÔÓ›·/ÙÚfiÌÔ˜64/21=85∞ÎÔ‹40 ÀÔÙÔÓ›·246™Ï‹Ó·˜36 ∞.2) OÍ›· ÂÁÎÂÊ·ÏÔ¿ıÂÈ·154 (4,3%) ¶¿ÁÎÚ·˜13 ∫ÒÌ·, Ï‹ı·ÚÁÔ˜86OÛÙ¿21 ¢È·Ù·Ú·¯‹ ÂȤ‰Ô˘ Û˘Ó›‰ËÛ˘, ¿ÓÔȘ68 °.2) ¢˘ÛÙÚÔÊ›·, ÛÙ·ÛÈÌfiÙËÙ· ‚¿ÚÔ˘˜309 (8,7%) B) ¢˘ÛÌÔÚʛ˜55°.3) ªÂÙ·‚ÔÏÈΤ˜ ‰È·Ù·Ú·¯¤˜260 (7,3%)
·ÛıÂÓ›˜ Ì ¯ÚfiÓÈ· Û˘ÌÙÒÌ·Ù· ‹ Û ÂÚ›Ô‰Ô ‡ÊÂÛ˘ ‹ ·Ô-
‰ÚÔÌ‹˜ Ù˘ ÎÏÈÓÈ΋˜ Û˘Ìو̷ÙÔÏÔÁ›·˜, ÂÍÂÙ¿ÛÙËÎ·Ó ‰Â›ÁÌ·Ù· Ô‡ÚˆÓ Ù˘ ÚÒÙ˘ ÚˆÈÓ‹˜ Ô‡ÚËÛ˘. ™Â ÂÚÈÔÚÈṲ̂ÓÔ
·ÚÈıÌfi ÂÚÈÙÒÛÂˆÓ (~2%) ÂÏ‹ÊıËÛ·Ó ‰Â›ÁÌ·Ù· Ô‡ÚˆÓ ˘fi
ÂÏÂÁ¯fiÌÂÓ˜ Û˘Óı‹Î˜. ¶·ÚÂÏ‹ÊıËÛ·Ó Ô‡Ú· ·ÛıÂÓÒÓ 2-6 ÒÚ˜ ÌÂÙ¿ ÙË ¯ÔÚ‹ÁËÛË Á‡̷ÙÔ˜ ‹ ÚˆÙ½Ó˘ (2 g/kg ‚¿ÚÔ˘˜) ‹ ÁÏ˘Îfi˙˘ (1,7 g/kg ‚¿ÚÔ˘˜) ‹ ·Ú·ÙÂٷ̤Ó˘ ÓËÛÙ›·˜, Ì ¯ÚÔÓÈ΋ ‰È¿ÚÎÂÈ· ·Ó¿ÏÔÁ· Ì ÙËÓ ËÏÈΛ· ÙÔ˘ ·ÛıÂÓÔ‡˜.
∏ ·Ó¿Ï˘ÛË ÙˆÓ ÔÚÁ·ÓÈÎÒÓ ÔͤˆÓ ÙˆÓ Ô‡ÚˆÓ ¤ÁÈÓ Ì ÙËÓ Ù¯ÓÈ΋ GC-MS Î·È ÂÊ·ÚÌfiÛÙËÎÂ Ë ÎÏ·ÛÈ΋ ÌÂıÔ‰ÔÏÔÁ›· Ù˘ ˘ÁÚ‹˜ Âί‡ÏÈÛ˘ Ì ÔÚÁ·ÓÈÎÔ‡˜ ‰È·Ï‡Ù˜ Î·È Ë ¯ËÌÈ΋ ·Ú·ÁÔÓÙÔÔ›ËÛ‹ ÙÔ˘˜ Û ÙÚÈÌÂı˘ÏÔÛ˘ÏÈÎÔ-ÂÓÒÛÂȘ (trimethylsilylation) (15). ∞ÍÈÔÏÔÁ‹ıËÎ·Ó Ù· ÔÚÁ·ÓÈο Ôͤ· ËÌÈ-
ÔÛÔÙÈο ‚¿ÛÂÈ Ù˘ ÎÚ·ÙÈÓ›Ó˘ ÙˆÓ Ô‡ÚˆÓ (mmol/mol ÎÚ·ÙÈÓ›Ó˘) Ì ÙË ¯Ú‹ÛË ÂÛˆÙÂÚÈÎÔ‡ ÚÔÙ‡Ô˘ Ô˘Û›·˜. ∏ ·Ó¿Ï˘ÛË
¤ÁÈÓ Û ·Ó·Ï˘Ù‹ Ù‡Ô˘ Carlo-Elba 2000, Fison’s MD800, Ù¯ÓÈ΋ ¤Á¯˘Û˘ splitless, Ù‡Ô˜ ÈÔÓÈÛÌÔ‡ electron-impact ηÈ
¯Ú‹ÛË ÛÙ‹Ï˘ ¯ÚˆÌ·ÙÔÁÚ·Ê›·˜ Ù‡Ô˘ BP-1 ‹ BP-5. ™Â 122 ·ÛıÂÓ›˜ Ì ÂÓ‰ÂÈÎÙÈο ÎÏÈÓÈο ‹ ÂÚÁ·ÛÙËÚȷο Â˘Ú‹Ì·Ù· ÔÚÁ·ÓÈ΋˜ Ô͢Ԣڛ·˜ ‹ ·Ó¿ÚÎÂÈ·˜ Ù˘ ‚-ÔÍ›‰ˆÛ˘ ÙˆÓ ÏÈ·ÚÒÓ ÔͤˆÓ, ÂÍÂÙ¿ÛÙËΠÙÔ Ê¿ÛÌ· ÙˆÓ Û˘Ó‰Â‰ÂÌ¤ÓˆÓ ·Î˘ÏÔηÚÓÈÙÈÓÒÓ (acyl-carnitine profile) ·fi ÛÙ·ÁfiÓ˜ ÍËÚÔ‡ ·›Ì·ÙÔ˜ Ì ÙË ÌÂıÔ‰ÔÏÔÁ›· (16) Tandem-MS (Û‡ÛÙËÌ· ‰‡Ô Ê·ÛÌ·ÙÔÁÚ¿ÊˆÓ Ì·˙ÒÓ), ÛÂ Û˘ÓÂÚÁ·Û›· Ì ÂȉÈο ÂÚÁ·ÛÙ‹ÚÈ· ÙÔ˘ Â͈ÙÂÚÈÎÔ‡. ∏ ÙÂÏÈ΋ ÙÂÎÌËÚ›ˆÛË ÙÔ˘ ˘Â‡ı˘ÓÔ˘ ÂÓ‰ÔÁÂÓÔ‡˜ ÌÂÈÔÓÂÎÙÈÎÔ‡ ÌÂÙ·‚ÔÏÈÛÌÔ‡ ¤ÁÈÓ Ì ÙË Ì¤ÙÚËÛË Ù˘ ‰Ú·ÛÙÈÎfiÙËÙ·˜ ÙˆÓ ÂÓ¯fiÌÂÓˆÓ ÂÓ˙‡ÌˆÓ ‹ Î·È ÙË ÁÔÓȉȷ΋ ·Ó¿Ï˘ÛË ÙˆÓ
·ıÔÁfiÓˆÓ ÌÂÙ·ÏÏ¿ÍÂˆÓ ·fi ÂÍÂȉÈÎÂ˘Ì¤Ó· ÂÚÁ·ÛÙ‹ÚÈ· ÙÔ˘
Â͈ÙÂÚÈÎÔ‡, Ì ·ÍÈfiÈÛÙ˜ ·Ó·Ï˘ÙÈΤ˜ Ù¯ÓÈΤ˜ (13). ÀÏÈÎfi Ù˘ ·Ó¿Ï˘Û˘ ‹Ù·Ó ·ÙÙ·Ú· ÙˆÓ ·ÛıÂÓÒÓ ·fi ‚ÈÔ„›· ‰¤ÚÌ·ÙÔ˜, ‹·ÙÔ˜ ‹ ·ÙÙ·Ú· ÂÚÈÊÂÚÈÎÔ‡ ·›Ì·ÙÔ˜. ∞ÔÙÂϤÛÌ·Ù·
ÙȘ ·Ó·Ï‡ÛÂȘ ‰È·ÈÛÙÒıËÎ·Ó ‰È·ÁÓˆÛÙÈΤ˜
ÌÂÙ·‚ÔÏÈÎÔ‡ ÓÔÛ‹Ì·ÙÔ˜ ÛÂ 85 Û˘ÓÔÏÈ-
·ÛıÂÓ›˜, Û 10 ÂÎ ÙˆÓ ÔÔ›ˆÓ, fï˜, Ë ‰È¿ÁÓˆÛË Ù˘ ÓfiÛÔ˘ ›¯Â ‹‰Ë ÙÂı› ·fi ÚÔÁÂÓ¤ÛÙÂÚ˜
ÂÚÁ·ÛÙËÚ›ˆÓ ÙÔ˘ Â͈ÙÂÚÈÎÔ‡ ÙËÓ ›‰È· ¯ÚÔÓÈ΋ ÂÚ›Ô‰Ô (¶›Ó·Î·˜ 2). ∂ȉÈÎfiÙÂÚ·, ‰È·ÈÛÙÒıËÎ·Ó Û 65 ·ÛıÂÓ›˜, 16 ‰È·ÊÔÚÂÙÈΤ˜ ÂÓ˙˘ÌÈΤ˜ ‹ ÚˆÙÂ˚ÓÈΤ˜ ·Ó¿ÚÎÂȘ, Ì ¯·Ú·ÎÙËÚÈÛÙÈ΋ ·¤ÎÎÚÈÛË ÔÚÁ·ÓÈÎÒÓ ÔͤˆÓ (¶›Ó·Î·˜ 2, ÓÔÛ‹Ì·Ù· 1-16). OÈ ·Ó·Ï‡ÛÂȘ ÙˆÓ ·Î˘ÏÔηÚÓÈÙÈÓÒÓ ·›Ì·ÙÔ˜
¤ÁÈÓ·Ó Û 25 ·fi ÙÔ˘˜ 65 ·ÛıÂÓ›˜ Î·È ¤‰ÂÈÍ·Ó Â›Û˘ ·ıÔÏÔÁÈΤ˜ ‰È·ÁÓˆÛÙÈΤ˜ ‰È·Ù·Ú·¯¤˜ (¶›Ó·Î·˜ 2, ÓÔÛ‹Ì·Ù· 5-9, 13-15). ŸÏÔÈ ÔÈ ·ÛıÂÓ›˜ ÂΉ‹ÏˆÓ·Ó Û˘Ìو̷ÙÔÏÔÁ›· ÛÙ· Ï·›ÛÈ· ÙˆÓ ÎÏÈÓÈÎÒÓ Ê·ÈÓÔÙ‡ˆÓ ÙˆÓ ·ÓÙ›ÛÙÔȯˆÓ ÓÔÛËÌ¿ÙˆÓ. ∏ ÂÓ˙˘ÌÈ΋ ‹/Î·È Ë ÁÔÓȉȷ΋ Ù·˘ÙÔÔ›ËÛË ÙˆÓ ·Ó·ÚÎÂÈÒÓ Ù˘ ÔÚÁ·ÓÈ΋˜ Ô͢Ԣڛ·˜ ¤ÁÈÓ Û ÙÔ˘Ï¿¯ÈÛÙÔÓ 46 ÂÚÈÙÒÛÂȘ ·ÛıÂÓÒÓ. ™Â fiÏÔ˘˜ ÙÔ˘˜ ·ÛıÂÓ›˜, Ë ÔÚÁ·ÓÈ΋ Ô͢Ԣڛ· ¤¯ÂÈ ÂȂ‚·Èˆı› Ì Ӥ˜ ·Ó·Ï‡ÛÂȘ. ™Ù· ÓÔÛ‹Ì·Ù· Ù˘ 2-L-˘‰ÚÔ͢ÁÏÔ˘Ù·ÚÈ΋˜ Ô͢Ԣڛ·˜ Î·È Âı˘ÏÔÌ·ÏÔÓÈ΋˜ ÂÁÎÂÊ·ÏÔ¿ıÂÈ·˜, ÛÙ· ÔÔ›· ‰ÂÓ ¤¯ÂÈ Ù·˘ÙÔÔÈËı› ˘Â‡ı˘ÓË ·Ó¿ÚÎÂÈ· ÂÓ˙‡ÌÔ˘, ÚˆÙ½Ó˘ ‹ ÁÔÓȉȷ΋˜ ÌÂÙ¿ÏÏ·Í˘, Ë ÓfiÛÔ˜ ÂȂ‚·ÈÒıËΠ̠ÙËÓ
·Ó¿Ï˘ÛË ÙˆÓ ‰ÂÈÁÌ¿ÙˆÓ Ô‡ÚˆÓ Î·È ·fi ¿ÏÏÔ ÂÍÂȉÈÎÂ˘Ì¤ÓÔ ÂÚÁ·ÛÙ‹ÚÈÔ.
∏ ·Ó¿Ï˘ÛË Ô‡ÚˆÓ ·fi 14 ·ÛıÂÓ›˜ ·ÔÎ¿Ï˘„ ·‡ÍËÛË ÙÔ˘ Á·Ï·ÎÙÈÎÔ‡ ÔͤԘ Î·È ‰È·Ù·Ú·¯¤˜ ÛÙ·
ÔÚÁ·ÓÈο Ôͤ· ÙÔ˘ ÙÚÈηڂÔ͢ÏÈÎÔ‡ ·ÎÏÔ˘, ¢ڋ-
Ì·Ù· ÂÓ‰ÂÈÎÙÈο ÌÂÙ·‚ÔÏÈ΋˜ ‰È·Ù·Ú·¯‹˜ Ù˘ ÔÌ¿‰·˜ ÙˆÓ ÂÓ˙˘ÌÈÎÒÓ ·Ó·ÚÎÂÈÒÓ Ù˘ Á·Ï·ÎÙÈ΋˜ ÌÂÙ·‚ÔÏÈ΋˜ ÔͤˆÛ˘. ∏ ÂȉÈÎfiÙÂÚË ‰ÈÂÚ‡ÓËÛË ÛÂ
¶›Ó·Î·˜ 2. ªÂÙ·‚ÔÏÈΤ˜ ·Ó¿ÚÎÂȘ ·ÛıÂÓÒÓÌ ÔÚÁ·ÓÈ΋ Ô͢Ԣڛ·,ÔÈ ÔÔ›ÔÈ ‰È·ÁÓÒÛÙËηÓÙËÓ ÂÚ›Ô‰Ô 1996-2001 ¡fiÛËÌ·∞ÛıÂÓ›˜∂Ȃ‚·›ˆÛË∂Ó ˙ˆ‹∞‚›ˆÛ·Ó∂Ó˙˘ÌÈ΋°ÔÓȉȷΤ˜ ÓfiÛÔ˘·Ó¿ÚÎÂÈ·ÌÂÙ·ÏÏ¿ÍÂȘ
1.∞ÏηÙÔÓÔ˘Ú›·5-23-2.ÀÂÚ·Ì̈ÓÈ·ÈÌ›·,ÔÚÔÙÈ΋ Ô͢Ԣڛ·10----O∆C deficiency(5+2*)12452 ASS deficiency(1)--111 LPI disorder(2)240-4 3.MSUD303034.T˘ÚÔÛÈÓ·ÈÌ›· (π)111115·.MMA mut7-2245‚.Adocbl(A)011-16.¶ÚÔÈÔÓÈ΋ Ô͢Ԣڛ·2+1**11237.HMGlyase-deficiency20202™Â ÂͤÏÈÍË 8.‚-ÎÂÙÔıÈÔÏ¿ÛË101019.°ÏÔ˘Ù·ÚÈ΋ Ô͢-(I)4260310.Canavan disease202022 11.SSADH-deficiency605055 12.L-2-OH-GA3120-13.MADD100110 14.MCAD616007 15.EPEMA syndrome1010∂ÚÂ˘Ó¿Ù·È¢È·Ù·Ú·¯¤˜, DCA+AC+ηÚÓÈÙ›Ó˘50---™‡ÓÔÏÔ5910
°·Ï·ÎÙÈ΋ ÌÂÙ·‚ÔÏÈ΋ ÔͤˆÛË140--1216.DPD deficiency101011 ¢È·Ù·Ú·¯¤˜ Ô˘ÚÈÓÒÓ10-1-™‡ÓÔÏÔ751042154521
O∆C: ÔÚÓ˘ı˘ÏÔηڂ·ÌÈÏÔ-ÙÚ·ÓÛÊÂÚ¿ÛË
ASS: Û˘ÓıÂÙ¿ÛË ·ÚÁÈÓÈÓÔËÏÂÎÙÚÈÎÔ‡ ÔͤԘ
LPI: ‰˘Û·ÓÂÍ›· Ù˘ Ï˘Û›Ó˘
MSUD: ÓfiÛÔ˜ Ì ÔÛÌ‹ ·fi ÛÈÚfiÈ ÛÊÂÓ‰¿ÌÔ˘ ÙˆÓ Ô‡ÚˆÓ
MMA mut: ÌÂı˘ÏÔÌË(·)ÏÔÓÈ΋ Ô͢Ԣڛ· ·Ó¿ÚÎÂÈ· ÌÔ˘Ù¿Û˘
Adocbl(A): ·Ó¿ÚÎÂÈ· ·‰ÂÓÔÛ˘ÏÔÎÔ‚·Ï·Ì›Ó˘ ∞
HMGlyase: 3-˘‰Úfi͢-3-ÌÂı˘ÏÔ-ÁÏÔ˘Ù·ÚÈ΋˜ Ï˘¿Û˘
SSADH: ‰Â¸‰ÚÔÁÂÓ¿ÛË Ù˘ ËÌȷω¸‰Ë˜ ÙÔ˘ ËÏÂÎÙÚÈÎÔ‡ Ôͤˆ˜
L-2-OH-GA: L-2-˘‰Úfi͢-ÁÏÔ˘Ù·ÚÈ΋ Ô͢Ԣڛ·
DPD deficiency: ·Ó¿ÚÎÂÈ· ‰Â¸‰ÚÔÁÂÓ¿Û˘ ÙˆÓ ‰È¸‰ÚÔ˘ÚÈÌȉÈÓÒÓ
MADD: ·Ó¿ÚÎÂÈ· ÔÏÏ·ÏÒÓ ‰Â¸‰ÚÔÁÂÓ·ÛÒÓ
MCAD: ·Ó¿ÚÎÂÈ· ‰Â¸‰ÚÔÁÂÓ¿Û˘ ÏÈ·ÚÒÓ ÔͤˆÓ ̤Û˘ ·Ï‡ÛÔ˘
EPEMA syndrÔme: Û‡Ó‰ÚÔÌÔ ÂÁÎÂÊ·ÏÔ¿ıÂÈ·˜-Âı˘ÏÔÌ·ÏÔÓÈ΋˜ Ô͢Ԣڛ·˜
DCA: ‰ÈηڂÔ͢ÏÈ΋ Ô͢Ԣڛ·
AC: ·Î˘ÏÔηÚÓÈÙ›Ó˜ * ÂÙÂÚÔ˙˘ÁÒÙ˜ ÌËÙ¤Ú˜ Ì ıÂÙÈο Â˘Ú‹Ì·Ù· Ù˘ ·Ó¿ÚÎÂÈ·˜ ** ·ÛıÂÓ‹˜ Ì ۷ʤ˜ Ê¿ÛÌ· ÔÚÁ·ÓÈÎÒÓ ÔͤˆÓ Î·È ÎÏÈÓÈÎfi ÂÂÈÛfi‰ÈÔ, ¯ˆÚ›˜ ÙÂÏÈ΋ ÂȂ‚·›ˆÛË
¤Ó·Ó ·ÛıÂÓ‹, Ô ÔÔ›Ô˜ ·Â‚›ˆÛÂ, Ô ¤ÏÂÁ¯Ô˜ ÛÙ·
Ô‡Ú· ·ÔÎ¿Ï˘„ ‰È·Ù·Ú·¯¤˜ ÙÔ˘ ÌÂÙ·‚ÔÏÈÛÌÔ‡
ÙˆÓ Ô˘ÚÈÓÒÓ. ™Â 5 ·ÛıÂÓ›˜, Ë ·Ó¿Ï˘ÛË ÙˆÓ ·Î˘-
ÏÔηÚÓÈÙÈÓÒÓ ¤‰ÂÈÍ ·ıÔÏÔÁÈο Â˘Ú‹Ì·Ù·, ÂÓ‰ÂÈ-
ÎÙÈο ·Ó¿ÚÎÂÈ·˜ Ù˘ ‚-ÔÍ›‰ˆÛ˘ ÙˆÓ ÏÈ·ÚÒÓ
ÔͤˆÓ ÛÙ· ÌÈÙÔ¯fiÓ‰ÚÈ·. ∞˘ÙÔ› ÔÈ ·ÛıÂÓ›˜, ›Û˘
·ÚÔ˘Û›·Û·Ó ‰ÈηڂÔ͢ÏÈ΋ Ô͢Ԣڛ· Î·È ÌÂȈ̤ÓË Û˘ÁΤÓÙÚˆÛË Ù˘ ÂχıÂÚ˘ Î·È ÔÏÈ΋˜ ηÚÓÈÙ›Ó˘ ÛÙÔ ·›Ì· (¶›Ó·Î·˜ 2). ¢ÂÓ ÂÍÂÙ¿ÛıËÎÂ, fï˜, ÂÚ·ÈÙ¤Úˆ Ë Èı·Ó¿ ˘Â‡ı˘ÓË ÂÓ˙˘ÌÈ΋ ·Ó¿ÚÎÂÈ·. ™Â ¿ÏÏÔ˘˜ 5 ·ÛıÂÓ›˜, Ë ·‡ÍËÛË ÙˆÓ ·Î˘ÏÔηÚÓÈÙÈÓÒÓ ÙÔ˘ ·›Ì·ÙÔ˜ ‰ÂÓ ‰È¢ÎÚÈÓ›ÛÙËΠ̠Â-
Ú·ÈÙ¤Úˆ ·Ó·Ï‡ÛÂȘ. ∂›Û˘, Ë ·Ó¿Ï˘ÛË ÙˆÓ ÔÚÁ·-
ÓÈÎÒÓ ÔͤˆÓ ·Ó¤‰ÂÈÍ ‰È·Ù·Ú·¯¤˜ ÙÔ˘ ›‰Ô˘˜ ηÈ
Ù˘ Û˘ÁΤÓÙÚˆÛ˘ ÙˆÓ ÔÚÁ·ÓÈÎÒÓ ÔͤˆÓ Û 247 ·ÛıÂÓ›˜ (5,3% ÙˆÓ ÂÍÂÙ·Ûı¤ÓÙˆÓ ‰ÂÈÁÌ¿ÙˆÓ) (¶›Ó·Î·˜ 3), ÛÙÔ˘˜ ÔÔ›Ô˘˜ Ô Â·Ó¤ÏÂÁ¯Ô˜ Î·È Ë ‰ÈÂÚ‡ÓËÛË Èı·Ó‹˜ ÂÓ˙˘ÌÈ΋˜ ·Ó¿ÚÎÂÈ·˜ ∫ª¡ ‰ÂÓ ÚÔ¯ÒÚËÛ ÂÚ·ÈÙ¤Úˆ. OÈ ÎÏÈÓÈΤ˜ ÂΉËÏÒÛÂȘ ÛÙȘ ηÙËÁÔڛ˜ ∞.1, µ Î·È °.2 ÛÙÔÓ ¶›Ó·Î· 1 ·Ó·Ê¤ÚÔÓÙ·È Û ̷ÎÚÔ¯ÚfiÓÈ· ‰È¿ÚÎÂÈ· Ù˘ ÓfiÛÔ˘ (>6 Ì‹Ó˜). OÈ ·ÛıÂÓ›˜ ·˘ÙÔ› ·ÔÙÂÏÔ‡Ó ¿Óˆ ·fi ÙÔ 60% ÙˆÓ ÂÍÂÙ·Ûı¤ÓÙˆÓ ÛÙËÓ ·ÚÔ‡Û· ÌÂϤÙË. ∏ ‰ÈÂÚ‡ÓËÛË Ô˘ ¤ÁÈÓ ÛÂ
Ô˘ ΢ڛˆ˜ ·Ó·Ê¤ÚÔÓÙ·È ÛÙȘ ηÙËÁÔڛ˜ ∞.2, °.1, °.3, ·ÚÔ˘Û›·Û·Ó 908 ·ÛıÂÓ›˜ (25% ÙˆÓ ·Ó·ÊÂÚÔ̤ӈÓ). ∞fi ÙË ‰ÈÂÚ‡ÓËÛË ·˘Ù‹˜ Ù˘ ÔÌ¿‰·˜
ÂΉËÏÒÛˆÓ, ‰È·ÈÛÙÒıËΠ‰È·ÁÓˆÛÙÈ΋ ÔÚÁ·ÓÈ΋
Ô͢Ԣڛ· Û 51 ·ÛıÂÓ›˜. ∏ ‰È¿ÎÚÈÛË Î·È Ù·ÍÈÓfiÌËÛË ÙˆÓ ·ÛıÂÓÒÓ Ô˘ ·ÚÔ˘Û›·˙·Ó ‰È·Ï›ԢÛ˜ ‹
‹È˜ ÂΉËÏÒÛÂȘ, ‰ÂÓ ¤ÁÈÓ ÛÙËÓ ·ÚÔ‡Û· ÌÂϤÙË.
ŸÌˆ˜, ÔÈ 7 ·fi ÙÔ˘˜ 85 ·ÛıÂÓ›˜ Ì ‰È·ÁÓˆÛÙÈ΋
ÔÚÁ·ÓÈ΋ Ô͢Ԣڛ· ‰ÈÂÚ¢ӋıËηÓ, ‰ÈfiÙÈ ·ÚÔ˘Û›·˙·Ó ‰È·ÏÂ›Ô˘Û· Û˘Ìو̷ÙÔÏÔÁ›· ÂΉËÏÒÛˆÓ. π‰È·›ÙÂÚË ·Í›· ¤¯Ô˘Ó Ù· ÛÙÔȯ›· Ù˘ ÔÚ›·˜
ÙˆÓ ·ÛıÂÓÒÓ ÌÂÙ¿ ÙË ‰È¿ÁÓˆÛË Ù˘ ÓfiÛÔ˘. ∞‚›ˆÛ·Ó 15 ·ÛıÂÓ›˜, 6 ÂÎ ÙˆÓ ÔÔ›ˆÓ ηٿ ÙËÓ Â-
Ú›Ô‰Ô ÙÔ˘ ÚÒÙÔ˘ ÂÂÈÛÔ‰›Ô˘ Ù˘ ÓfiÛÔ˘. OÈ 23
·fi ÙÔ˘˜ 42 ˙ÒÓÙ˜ ·ÛıÂÓ›˜ Ì ÁÓˆÛÙ‹ ÎÏÈÓÈ΋ Ô-
Ú›· ·ÚÔ˘ÛÈ¿˙Ô˘Ó ÛÔ‚·Ú‹ ÓÔÛËÚfiÙËÙ·.
™˘˙‹ÙËÛË
O ·ÚÈıÌfi˜ ÙˆÓ ·ÛıÂÓÒÓ Ô˘ ‰ÈÂÚ¢ӋıËÎ·Ó ÁÈ·
Èı·Ó‹ ÔÚÁ·ÓÈ΋ Ô͢Ԣڛ·, ·ÓÙÈÛÙÔȯ› ÛÙÔ 0,83% ÂÚ›Ô˘ ÙˆÓ ÁÂÓÓ‹ÛÂˆÓ ·˘Ù‹˜ Ù˘ ÂÚÈfi‰Ô˘ ÛÙË
¯ÒÚ·. ¢Â‰Ô̤ÓÔ˘ fiÙÈ Ë ‰ÈÂÚ‡ÓËÛË ÁÈ· Èı·Ó‹ ÔÚÁ·ÓÈ΋ Ô͢Ԣڛ· Ú·ÁÌ·ÙÔÔÈ‹ıËΠϋڈ˜ ÌfiÓÔ ·fi ÙË Û˘ÁÎÂÎÚÈ̤ÓË ÔÌ¿‰· ÛÙËÓ ∂ÏÏ¿‰·, ÙÔ Ì¤ÁÂıÔ˜ ÙˆÓ ÂÍÂÙ·Ûı¤ÓÙˆÓ Â›Ó·È ÂÓ‰ÂÈÎÙÈÎfi ÁÈ· ÙËÓ ÂÍ·ÁˆÁ‹ ¯Ú‹ÛÈÌˆÓ Û˘ÌÂÚ·ÛÌ¿ÙˆÓ. ŒÙÛÈ, ÔÈ ·Ó·ÊÂÚfiÌÂÓ˜ ‰ÈÂÚ¢ӋÛÂȘ ˘ÔÏ›ÔÓÙ·È ÙÔ˘ ÔÛÔÛÙÔ‡ ÙˆÓ ·ÛıÂÓÒÓ Ì ÎÏËÚÔÓÔÌÈο ÓÔÛ‹Ì·Ù· Ô˘ ÔÊ›ÏÔÓÙ·È Û ÌÔÓÔÁÔÓȉȷΤ˜ ·Ó¿ÚÎÂȘ (1% ÙˆÓ ÁÂÓÓ‹ÛˆÓ) (2). ÕÏψÛÙÂ, ÔÏÏÔ› ·ÛıÂÓ›˜ Ì ∫ª¡, ·ÏÏ¿ Î·È ¿Û¯ÔÓÙ˜ ·fi ¿ÏϘ ηÙËÁÔڛ˜ ÓÔÛËÌ¿ÙˆÓ, ·ÚÔ˘ÛÈ¿˙Ô˘Ó ÂÓ‰ÂÈÎÙÈΤ˜ ÎÏÈÓÈΤ˜ ÂΉËÏÒÛÂȘ Ô˘ ÂÈ‚¿ÏÏÔ˘Ó ÙË ‰ÈÂÚ‡ÓËÛË Èı·Ó‹˜ ÔÚÁ·ÓÈ΋˜ Ô͢Ԣڛ·˜. ∂›Û˘, ÂÎÙÈÌ¿Ù·È fiÙÈ ÛÙËÓ ·-
ÚÔ‡Û· ÌÂϤÙË, ÔÈ ·ÛıÂÓ›˜ Ô˘ ‰ÈÂÚ¢ӋıËÎ·Ó ÌÂ
Ôͤˆ˜ ¿Û¯ÔÓÙÔ˜ ·ÔÙÂÏÔ‡Ó ÌÈÎÚfi ÔÛÔÛÙfi Û¯ÂÙÈο Ì ÙÔ˘˜ ¯ÚfiÓÈ·˜ ‰È·‰ÚÔÌ‹˜ ¿Û¯ÔÓÙ˜. ∂ÈϤÔÓ, ·fi ÙËÓ Î·ıËÌÂÚÈÓ‹ ÂÌÂÈÚ›· ‰È·ÈÛÙÒÓÔ˘Ì fiÙÈ Ô ¤ÏÂÁ¯Ô˜ Èı·Ó‹˜ ÔÚÁ·ÓÈ΋˜
Ô͢Ԣڛ·˜ Û Ôͤˆ˜ ¿Û¯ÔÓÙ˜ ·ÛıÂÓ›˜ ‰ÂÓ Ù›ıÂÙ·È ¿ÓÙ· ÛÙË ‰È·ÊÔÚÈ΋ ‰È·ÁÓˆÛÙÈ΋ ÛΤ„Ë ÙˆÓ
·È‰È¿ÙÚˆÓ, fiˆ˜ ·Ó·Ê¤ÚÂÙ·È Î·È ‰ÈÂıÓÒ˜ (6). ∞Ó·-
ʤÚıËΠfiÙÈ ÙÔ 9,31% ÙÔ˘ Û˘ÓfiÏÔ˘ ÙˆÓ ÂÍÂÙ·Ûı¤ÓÙˆÓ ·ÛıÂÓÒÓ ‹Ù·Ó ÓÂÔÁÓÈ΋˜ ËÏÈΛ·˜, Û 11 ÂÎ ÙˆÓ
ÔÔ›ˆÓ Ù¤ıËÎÂ Ë ‰È¿ÁÓˆÛË Ù˘ ÓfiÛÔ˘. ∆Ô ÔÛÔÛÙfi
·˘Ùfi ÙˆÓ ·ÛıÂÓÒÓ ·Ê›ÛÙ·Ù·È ÛËÌ·ÓÙÈο ÙˆÓ ·ÛıÂ-
ÓÒÓ Ì ∫ª¡, ÔÈ ÔÔ›ÔÈ ·ÚÔ˘ÛÈ¿˙Ô˘Ó ÛÙË ÓÂÔÁÓÈ΋
ËÏÈΛ· ÎÏÈÓÈ΋ Û˘Ìو̷ÙÔÏÔÁ›·(ÙÔ ÔÛÔÛÙfiÊÙ¿-
ÓÂÈ ÛÙÔ 25% ÙˆÓ ·Û¯fiÓÙˆÓ ·fi ∫ª¡). ∂ÎÙfi˜ ÙÔ˘ ˘Ô‰ËÏÔ‡ÌÂÓÔ˘ ¯·ÌËÏÔ‡ ÔÛÔÛÙÔ‡ ÂÍÂÙ·˙fiÌÂÓˆÓ
ÁÈ· Èı·Ó‹ ÔÚÁ·ÓÈ΋ Ô͢Ԣڛ·, ÔÈ ÙÂı›Û˜ ‰È·ÁÓÒÛÂȘ Â›Ó·È ÔÛÔÛÙÈ·›· ÏÈÁfiÙÂÚ˜ ·fi ÙȘ ‰È·ÁÓÒÛÂȘ
Â˘Úˆ·˚ÎÒÓ ÂÚÁ·ÛÙËÚ›ˆÓ (17). ™˘ÁÎÂÎÚÈ̤ӷ, ÔÈ ‰È·ÁÓÒÛÂȘ ÙˆÓ 85 ÂÚÈÙÒÛÂˆÓ ∫ª¡ ·ÔÙÂÏÔ‡Ó ÙÔ 1,69% ÙÔ˘ Û˘ÓfiÏÔ˘ ÙˆÓ ÂÍÂÙ·Ûı¤ÓÙˆÓ
Ì ÙȘ ÙÂı›Û˜ ‰È·ÁÓÒÛÂȘ (¶›Ó·Î·˜ 2, ÓÔÛ‹Ì·Ù· 1-15), ÔÈ ÔÌ¿‰Â˜ ÙˆÓ ·Ó·ÚÎÂÈÒÓ ÙÔ˘ ÌÂÙ·‚ÔÏÈÛÌÔ‡ ÙˆÓ ÔÚÁ·ÓÈÎÒÓ ÔͤˆÓ, ·ÌÈÓÔ-ÔÍ˘Ô¿ıÂÈ·˜ ‹ ‰È·Ù·Ú·¯‹˜ ÙÔ˘ ·ÎÏÔ˘ Ù˘ Ô˘Ú›·˜, ‰È·ÈÛÙÒıËÎ·Ó Û 69 ·ÛıÂÓ›˜. ∏ ·ıÚÔÈÛÙÈ΋ Û˘¯ÓfiÙËÙ· ÙˆÓ ·Û¯fiÓÙˆÓ ·fi ·˘Ù¤˜ ÙȘ ·Ó¿ÚÎÂȘ
ÊÙ¿ÓÂÈ ÙË 1:8696 ÁÂÓÓ‹ÛÂȘ (Ì ‚¿ÛË ÙȘ 100.000 ÂÚ›Ô˘ ÁÂÓÓ‹ÛÂȘ ÂÙËÛ›ˆ˜ ÛÙË ¯ÒÚ·).
∂ȉÈÎfiÙÂÚ·, ÛËÌ·ÓÙÈ΋, ·ÏÏ¿ ÏÈÁfiÙÂÚÔ ·fi ÙȘ ·Ó·ÊÔÚ¤˜ ÛÂ Â˘Úˆ·˚Τ˜ ¯ÒÚ˜ Î·È ÛÙȘ ∏¶∞ (18), ·Ó·‰ÂÈÎÓ‡ÂÙ·È Ë Û˘¯ÓfiÙËÙ· ÙˆÓ ÓÔÛËÌ¿ÙˆÓ Ù˘ ÌÂı˘ÏÔÌ·ÏÔÓÈ΋˜ Î·È Ù˘ ÚÔÈÔÓÈ΋˜ Ô͢Ԣڛ·˜ ηÈ
¶›Ó·Î·˜ 3. ∂Ӊ›ÍÂȘ Èı·Ó‹˜ ÌÂÙ·‚ÔÏÈ΋˜ ·Ó¿ÚÎÂÈ·˜ ·fi ÙËÓ ·Ó¿Ï˘ÛË ÙˆÓ ÔÚÁ·ÓÈÎÒÓ ÔͤˆÓ ÙˆÓ Ô‡ÚˆÓ ÂÍÂÙ·Ûı¤ÓÙˆÓ ·ÛıÂÓÒÓ
∞ÍÈÔÏfiÁËÛË Â˘ÚËÌ¿ÙˆÓ Ù˘ ·Ó¿Ï˘Û˘∞ÛıÂÓ›˜ Ì ÂÓ‰ÂÈÎÙÈΤ˜ ‰È·Ù·Ú·¯¤˜
1.ªÂı˘ÏÔÌ·ÏÔÓÈ΋ Ô͢Ԣڛ· 15
2.¢ÈηڂÔ͢ÏÈ΋ Ô͢Ԣڛ· ‚-ÔÍ›‰ˆÛ˘ ÏÈ·ÚÒÓ ÔͤˆÓ58
3.OÚÔÙÈÎfi Ô͇, Èı·Ó‹˜ ·Ó¿ÚÎÂÈ·˜ ÙÔ˘ ·ÎÏÔ˘ Ù˘ Ô˘Ú›·˜10
4·.°·Ï·ÎÙÈ΋ ÌÂÙ·‚ÔÏÈ΋ ÔͤˆÛË: Á·Ï·ÎÙÈ΋ Ô͢Ԣڛ·33
4‚.∂Ó‰ÂÈÎÙÈΤ˜ ·ÓˆÌ·Ï›Â˜ ‰˘ÛÏÂÈÙÔ˘ÚÁ›·˜ Ù˘ ·Ó·Ó¢ÛÙÈ΋˜ ·Ï‡ÛÔ˘ ÙˆÓ ÌÈÙÔ¯ÔÓ‰Ú›ˆÓ41 4Á.¢È·Ù·Ú·¯¤˜ ÙÔ˘ ·ÎÏÔ˘ ÙˆÓ ÙÚÈηڂÔ͢ÏÈÎÒÓ ÔͤˆÓ19 5.O͢Ԣڛ· ÂÓ‰ÂÈÎÙÈ΋ ÁÏÔ˘Ù·ÚÈ΋˜ Ô͢Ԣڛ·˜ Ù‡Ô˘ π3
6.O͢Ԣڛ· ÂÓ‰ÂÈÎÙÈ΋ Ù˘ÚÔÛÈÓ·ÈÌ›·˜ Ù‡Ô˘ ππ3
7.∞‡ÍËÛË ˘‰ÚÔ͢-‰È·ÎÏ·‰ˆÙÈÎÒÓ ÔͤˆÓ ÂÓ‰ÂÈÎÙÈ΋ Èı·Ó‹˜ ÓfiÛÔ˘ ÔÛÌ‹˜ Ô‡ÚˆÓ Û·Ó ·fi ÛÈÚfiÈ ÛÊÂÓ‰¿ÌÔ˘5
8.3-ÌÂı˘ÏÔ-ÁÏÔ˘Ù·ÎÔÓÈ΋ Ô͢Ԣڛ·7
9.O͢Ԣڛ· ÂÓ‰ÂÈÎÙÈ΋ ‰È·Ù·Ú·¯‹˜ ÙˆÓ Ó¢Úԉȷ‚È‚·ÛÙÒÓ ÙÔ˘ ÌÂÙ·‚ÔÏÈÛÌÔ‡ Ù˘ ÓÙÔ·Ì›Ó˘2 10.O͢Ԣڛ· ÂÓ‰ÂÈÎÙÈ΋ Èı·Ó‹˜ ˘ÂÚÔÍ·ÏÔ˘Ú›·˜ Ù‡Ô˘ π3 11.O͢Ԣڛ· ÂÓ‰ÂÈÎÙÈ΋ ‰È·Ù·Ú·¯ÒÓ ‚-ÔÍ›‰ˆÛ˘ ÙˆÓ ˘ÂÚÔÍ˘ÛˆÌ¿ÙˆÓ6 12·.∞˘ÍË̤ÓË ·¤ÎÎÚÈÛË ÔÚÁ·ÓÈÎÒÓ ÔͤˆÓ ÌË ÂȉÈÎÔ‡ ÚÔÊ›Ï ‰˘ÛÏÂÈÙÔ˘ÚÁ›·˜24 12‚.ªÂÌÔӈ̤ÓË ·‡ÍËÛË ÙÈÁÏ˘ÏÔÁÏ˘Î›Ó˘10 12Á.ªÂÌÔӈ̤ÓË ·‡ÍËÛË 3-˘‰ÚÔ͢-ÈÛÔ‚·ÏÂÚÈÎÔ‡ ÔͤԘ8
·Ó¿ÚÎÂÈ· Ù˘ Ë·ÙÈ΋˜ Û˘ÓıÂÙ¿Û˘ (trimethyamine N-oxide), ‰ÈÌÂı˘ÏÔÁÏ˘ÎÈÓÔ˘Ú›· (dimethylglycinuria) Û ·Ó¿ÚÎÂÈ·Ù˘ ·Ê˘‰ÚÔÁÔÓ¿Û˘ (dimethylglycine dehydrogenase), ÌÂÈÔÓÂÎÙÈÎfi˜ ÌÂÙ·‚ÔÏÈÛÌfi˜ ÙˆÓ ¯ÔÏÈÎÒÓ ÔͤˆÓ Ì ·‡ÍËÛË ÂӉȿÌÂÛˆÓ ÚÔ˚fiÓÙˆÓ ÙÔ˘ ÌÂÙ·‚ÔÏÈÛÌÔ‡ ÙÔ˘˜, ÂÓ˙˘ÌÈ΋
·Ó¿ÚÎÂÈ· ÛÙÔÓ ÌÂÙ·‚ÔÏÈÛÌfi Ù˘ ÎÚ·ٛÓ˘ ÌÂ
·‡ÍËÛË ÛÙ· Ô‡Ú· ÙÔ˘ ÁÔ˘·ÓȉÈÓÔÍÂÈÎÔ‡ ÔͤԘ
(guanidino-acetate: GAMT deficiency). ∏ ·Ó¿Ú-
ÎÂÈ· ÙˆÓ ÂÓ˙‡ÌˆÓ ÙÔ˘ ÌÂÙ·‚ÔÏÈÛÌÔ‡ ÙˆÓ Ó¢Úԉȷ‚È‚·ÛÙÒÓ ÂϤÁ¯ÂÙ·È Ì ÙÔÓ ÔÛÔÙÈÎfi ÚÔÛ‰ÈÔÚÈÛÌfi
ÙÔ˘˜ ÛÙÔ ÂÁÎÂÊ·ÏÔÓˆÙÈ·›Ô ˘ÁÚfi Ô˘ÛÈÒÓ, fiˆ˜ ›-
Ó·È ÙÔ Á-·ÌÈÓÔ‚Ô˘Ù˘ÚÈÎfi Ô͇ (GABA), ÙÔ ÔÌÔ‚·Ï˘-
ÓÈÎfi Ô͇ (HVA), Ë ÓÙÔ·Ì›ÓË, ÙÔ 5-˘‰ÚÔ͢-ÈÓ‰ÔÏÔ-
ÔÍÈÎfi Ô͇ Î·È ÔÈ ÙÂÚ›Ó˜. ™¯ÂÙÈο, ··ÈÙÔ‡ÓÙ·È ÂÈ-
‰ÈΤ˜ Û˘Óı‹Î˜ Ï‹„ˆ˜ Î·È ·Ó¿Ï˘Û˘ ÙˆÓ ·ÓÙ›-
ÛÙÔȯˆÓ Ô˘ÛÈÒÓ (11).
∏ ÂÓ‰ÔÁÂÓ‹˜ ·Ù¤ÏÂÈ· Ù˘ Û˘ÓÂÚÁÈ΋˜ Ì ¤Ó˙˘Ì·
‰Ú¿Û˘ ÙˆÓ ‚ÈÙ·ÌÈÓÒÓ, fiˆ˜ Ù˘ ÎÔ‚·Ï·Ì›Ó˘, Ù˘
‚ÈÔÙÈÓȉ¿Û˘ Î·È Ù˘ ˘ÚȉÔ͛Ӣ, ÂϤÁ¯ÂÙ·È Ì ÂÈ-
‰È΋ ÁÈ· οı ÂÚ›ÙˆÛË Ì¤ıÔ‰Ô (13). O ÂÓ‰ÔÁÂÓ‹˜
ÌÂÈÔÓÂÎÙÈÎfi˜ ÌÂÙ·‚ÔÏÈÛÌfi˜ Ù˘ ÎÔ‚·Ï·Ì›Ó˘ ÂϤÁ-
¯ÂÙ·È ÂÌ̤ۈ˜ Ì ÙËÓ ·Ó›¯Ó¢ÛË Ù˘ ÌÂı˘ÏÔÌ·ÏÔ-
ÓÈ΋˜ Ô͢Ԣڛ·˜ Î·È ÔÌÔ΢ÛÙ˘ÓÔ˘Ú›·˜ (¶›Ó·Î·˜ 2,
·ÛıÂÓ‹˜ 5‚). ∏ ·Ó¿ÚÎÂÈ· Û˘ÌÌÂÙÔ¯‹˜ Ù˘ ˘ÚÈ-
‰Ô͛Ӣ ÛÙÔÓ ÌÂÙ·‚ÔÏÈÛÌfi ÙÔ˘ GABA ÛÙȘ ÂÁÎÂÊ·-
ÏÈΤ˜ ÏÂÈÙÔ˘ÚÁ›Â˜ ‰È·ÈÛÙÒÓÂÙ·È ÂÌ̤ۈ˜, Ì ÙËÓ
¿ÌÂÛË ˘Ô¯ÒÚËÛË ÙˆÓ ÂÂÈÛÔ‰›ˆÓ Û·ÛÌÒÓ ÌÂÙ¿
ÙË ¯ÔÚ‹ÁËÛ‹ Ù˘. ∏ ·Ó·Ú΋˜ ÂÓ˙˘ÌÈ΋ ‰Ú¿ÛË
Ù˘ ‚ÈÔÙÈÓȉ¿Û˘ ÚÔÛ‰ÈÔÚ›˙ÂÙ·È Û¯ÂÙÈο ‡ÎÔÏ·
Û ‰Â›ÁÌ· ·›Ì·ÙÔ˜ ÙÔ˘ ·ÛıÂÓÔ‡˜. ∂Ó‰ÂÈÎÙÈο, ÂϤÁ-
¯ÔÓÙ·È ÔÈ Û˘ÁÎÂÓÙÚÒÛÂȘ ÙÔ˘ Á·Ï·ÎÙÈÎÔ‡ ÔͤԘ ÛÙÔ
·›Ì· Î·È ÛÙÔ ∂¡À,Î·È ÛÙ· Ô‡Ú· ÙÔ Ê¿ÛÌ· ÙˆÓ ÔÚ-
Á·ÓÈÎÒÓ ÔͤˆÓ, Ù· ÔÔ›· Û˘Ó‹ıˆ˜ Â›Ó·È ·ıÔÏÔÁÈ-
ο ÙËÓ ÂÚ›Ô‰Ô ÙˆÓ ÂÂÈÛÔ‰›ˆÓ Ù˘ ÓfiÛÔ˘. ¶·Ú’ fiÙÈ Ë Û˘¯ÓfiÙËÙ· Ù˘ ·Ó¿ÚÎÂÈ·˜ ·˘Ù‹˜ ÛÙËÓ ∂˘ÚÒË
‰ÂÓ Â›Ó·È Ôχ Û¿ÓÈ· (1:60-100 ¯ÈÏÈ¿‰Â˜ ÁÂÓÓ‹ÛÂȘ), ·fi ÙȘ ·ÓˆÙ¤Úˆ ·Ó·Ï‡ÛÂȘ ‰ÂÓ ‰È·ÈÛÙÒıËΠÂÓ‰ÂÈÎÙÈ΋ Ô͢Ԣڛ·. ∞ӷχÛÂȘ ÔÚÁ·ÓÈÎÒÓ Ôͤ-
ˆÓ ·fi 42 ·ÛıÂÓ›˜ (¶›Ó·Î·˜ 3, ¡Ô 12) ·ÚÔ˘Û›·-
Û·Ó ·‡ÍËÛË Û ÔÚÈṲ̂ӷ ÂÍ ·˘ÙÒÓ, Ô˘ ‰ÂÓ ÙÂÎÌË-
ÚÈÒÓÔ˘Ó ÂȉÈ΋ ÂÈÎfiÓ· ÂÓ‰ÔÁÂÓÔ‡˜ ÂÓ˙˘ÌÈ΋˜ ·ÓÂ-
¿ÚÎÂÈ·˜. ™˘¯Ó¿, ÂÓ‰ÔÁÂÓ‹ ÌÂÙ·‚ÔÏÈο ÓÔÛ‹Ì·Ù·
›Ù ÌÂÌÔӈ̤Ó˜ ÔÚÁ·ÓÈΤ˜ ‚Ï¿‚˜, fiˆ˜ ÙÔ˘
‹·ÙÔ˜, ÙˆÓ ÓÂÊÚÒÓ, ÙÔ˘ ÂÓÙ¤ÚÔ˘ ‹ Ë Ï‹„Ë Ê·Ú-
Ì¿ÎˆÓ Î·È ÂȉÈ΋˜ ‰È·ÙÚÔÊ‹˜, ·ÚÔ˘ÛÈ¿˙Ô˘Ó ‰È·Ù·-
Ú·¯¤˜ ÙˆÓ ÔÚÁ·ÓÈÎÒÓ ÔͤˆÓ, Ë ·ÍÈÔÏfiÁËÛË ÙˆÓ
ÔÔ›ˆÓ Â›Ó·È ·ÌÊ›‚ÔÏË (8,12).
¶ÔÏÏ¿ ·Ú·ÂÌÙÈο Ô˘ Û˘ÓÔ‰Â‡Ô˘Ó Ù· ‰Â›ÁÌ·Ù· ·ÛıÂÓÒÓ, ·Ó·Ê¤ÚÔ˘Ó ÙËÓ ÎÏÈÓÈ΋ ÙÔ˘˜ ηٿÛÙ·ÛË Ì ÁÂÓÈÎÔ‡˜ fiÚÔ˘˜, fiˆ˜ ·Ó·Ù˘Íȷ΋ Î·È „˘¯ÔÎÈÓËÙÈ΋ ηı˘ÛÙ¤ÚËÛË, ·Ó·Ù˘ÍȷΤ˜ ·ÓˆÌ·Ï›Â˜ ÙÔ˘ ÂÁÎÂÊ¿ÏÔ˘, ÂÁÎÂÊ·ÏÈ΋
Ï˘ÔÚÁ·ÓÈΤ˜ ‚Ï¿‚˜, ÂÈÏË„›·, ‚ÚÂÊÈ΋ ˘ÔÙÔÓ›·, ÏÔÈÌÒÍÂȘ (18). ∞˘Ù¤˜ ÔÈ ÁÂÓÈΤ˜ ·Ó·ÊÔÚ¤˜ ‰È·Ù·Ú·¯ÒÓ, ·Ó Î·È ‰ÂÓ ·ÔÙÂÏÔ‡Ó Î‡ÚÈ· ÎÏÈÓÈ΋ ÂΉ‹ÏˆÛË ÔÚÁ·ÓÈ΋˜ Ô͢Ԣڛ·˜, ÔÚÈṲ̂Ó˜ ÊÔÚ¤˜ ÔÊ›ÏÔÓÙ·È Û ∫ª¡. ∏ ÂÚ·ÈÙ¤Úˆ ηÙ‡ı˘ÓÛË Ù˘
‰ÈÂÚ‡ÓËÛ˘ ηıÔÚ›˙ÂÙ·È Ì ÙËÓ ·Ó·ÊÔÚ¿ ÂÚÈÛÛfiÙÂÚˆÓ ÛÙÔȯ›ˆÓ ÙˆÓ ·ÛıÂÓÒÓ.
™˘ÌÂÚ·ÛÌ·ÙÈο, Ù· ·ÓˆÙ¤Úˆ ·Ó·‰ÂÈÎÓ‡Ô˘Ó ÂÓ
̤ÚÂÈ ÙÔ Ì¤ÁÂıÔ˜ Î·È Ù· ‰È·ÁÓˆÛÙÈο ÚÔ‚Ï‹Ì·Ù·
ÙˆÓ ÂÏÂÁ¯fiÌÂÓˆÓ ÓÔÛËÌ¿ÙˆÓ ÛÙÔÓ ÂÏÏËÓÈÎfi ÏËı˘ÛÌfi. ∏ ·ÎÚÈ‚‹˜ ·ÔÙ‡ˆÛË Ù˘ Û˘¯ÓfiÙËÙ·˜ ·˘ÙÒÓ ÙˆÓ ÓÔÛËÌ¿ÙˆÓ, fiˆ˜ Î·È Ë ÏËÚ¤ÛÙÂÚË ÂÍ·ÁˆÁ‹ Û˘ÌÂÚ·ÛÌ¿ÙˆÓ ·fi ÙËÓ ÂÊ·ÚÌÔÁ‹ Ù˘ È·ÙÚÈ΋˜
·Ú¤Ì‚·Û˘ ÛÙÔ˘˜ ÂÏÂÁ¯fiÌÂÓÔ˘˜ ·ÛıÂÓ›˜, ÌÔÚÔ‡Ó Ó· ÂÈÙ¢¯ıÔ‡Ó Ì ÙËÓ ÂÚ·ÈÙ¤Úˆ ·Ó¿Ù˘ÍË ÙˆÓ ÂÍÂȉÈÎÂ˘Ì¤ÓˆÓ È·ÙÚÈÎÒÓ ÌÔÓ¿‰ˆÓ ‰È¿ÁÓˆÛ˘, ·ÁˆÁ‹˜ Î·È ¤Ú¢ӷ˜ ÛÙË ¯ÒÚ· Ì·˜.
∂˘¯·ÚÈÛٛ˜
∂˘¯·ÚÈÛÙԇ̠ÂηÙÔÓÙ¿‰Â˜ È·ÙÚÔ‡˜ ·fi fiÏ· Ù· ÓÔÛÔÎÔÌ›· Ù˘ ¯ÒÚ·˜, ÔÈ ÔÔ›ÔÈ ÛÙË ¯ÚÔÓÈ΋ ÂÚ›Ô‰Ô 1996-2001 Ì¿˜ ·¤ÛÙÂÈÏ·Ó ‰Â›ÁÌ·Ù· ÙˆÓ ·ÛıÂÓÒÓ Ì·˙› Ì ÂÓËÌÂÚˆÙÈο
ÛËÌÂÈÒÌ·Ù·. ∂›Û˘, ¢¯·ÚÈÛÙԇ̠ÙËÓ Î·. ∂. ªÈ¯ÂϷοÎË, ηıÒ˜ Î·È ÙÔ ˘fiÏÔÈÔ ÂÈÛÙËÌÔÓÈÎfi ÚÔÛˆÈÎfi ÙÔ˘ πÓÛÙÈÙÔ‡ÙÔ˘ ÀÁ›·˜ ÙÔ˘
1. Scriver CR. Garrrod’s foresight: our hindsight. J Inherit Metab Dis 2001;24:93-116.
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10. ª·ÙÛ·ÓÈÒÙ˘ ¡, ∫·Ú¿ıÈÔ˜ £ Î·È Û˘Ó. ™‡ÌÊ˘Ù˜ ‰È·Ù·Ú·¯¤˜ ÙÔ˘ ÌÂÙ·‚ÔÏÈÛÌÔ‡. ™ÙÔ: ª·ÙÛ·ÓÈÒÙ˘. ¶·È‰È·ÙÚÈ΋, ∆fiÌÔ˜ ππ. 1Ë ÂΉ. ∞ı‹Ó·: ∂ΉfiÛÂȘ §›ÙÛ·˜; 1999. ÛÂÏ. 8961130.
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14. Vreken P, van Lint AE, Bootsma AH, Overmars H, Wanders RJ, van Gennip AH. Rapid diagnosis of organic acidemias and fatty-acid oxidation defects by quantitative electrospray tandem-MS acyl-carnitine analysis in plasma. Adv Exp Med Biol 1999;466:327-337.
15. Tanaka K, Hine DG. Compilation of gas chromatographic retention indices of 163 metabolically important organic acids, and their use in detection of patients with organic acidurias. J Chromatogr 1982;239:301-322.
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19. Gibson KM, Hoffmann GF, Hodson AK, Bottiglieri T, Jakobs C. 4-Hyrdoxybutyric acid and the clinical phenotype of succinic semialdehyde dehydrogenase deficiency, an inborn error of GABA metabolism. Neuropediatrics 1998;29:14-22.
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27. Evangeliou A, Lionis C, Michailidou H, Spilioti M, Kanitsakis A, Nikitakis P et al. Selective screening for inborn errors of metabolism: the primary care-based model in rural Crete. J Inherit Metab Dis 2001;24:877-880.
28. ¶ÂÙÚ›‰Ô˘ E, ∫·Ú¿ıÈÔ˜ £, ∆ÚȯfiÔ˘ÏÔ˜ ¢ ÂÈÛÙËÌÔÓÈÎÔ› Û˘ÓÙÔÓÈÛÙ¤˜. ¶ÚÔÛ˘Ìو̷ÙÈÎfi˜ ¤ÏÂÁ¯Ô˜ ·È‰ÈÒÓ Î·È ÂÊ‹‚ˆÓ. ∂Ó‰ÔÁÂÓ›˜ ‰È·Ù·Ú·¯¤˜ ÙÔ˘ ÌÂÙ·‚ÔÏÈÛÌÔ‡. ∞ı‹Ó·: ∑‹Ù·; 1999. ÛÂÏ. 88-90.
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HÌÂÚÔÌËÓ›· ˘Ô‚ÔÏ‹˜: 22-10-2002
HÌÂÚÔÌËÓ›· ¤ÁÎÚÈÛ˘: 10-01-2003
¢È‡ı˘ÓÛË ·ÏÏËÏÔÁÚ·Ê›·˜: °ÂÒÚÁÈÔ˜ ¢. ª·ÚfiÔ˘ÏÔ˜
µÈÔ·ıÔÏfiÁÔ˜, ∂ÈÌÂÏËÙ‹˜ ∞’
ª·Î‰ÔÓ›·˜ 56, ¡. ∏Ú¿ÎÏÂÈÔ, ∞ÙÙÈ΋
∂ƒ∂À¡∏∆π∫∏
∞ÍÈÔÏfiÁËÛË
Ù˘ Û˘ÌÌfiÚʈÛ˘ ÛÙË ıÂڷ›· ·ÔÛȉ‹ÚˆÛ˘
Û ·È‰È¿ Ô˘ ¿Û¯Ô˘Ó ·fi ÔÌfi˙˘ÁË
∫. ¶··‰ÔÔ‡ÏÔ˘ - §ÂÁ̤ÏÔ˘1, ª. ∞ı·Ó·Û›Ô˘ - ªÂÙ·Í¿2, °. µ·ÚÏ¿Ì˘3, ™. ∫·Ú·Ì¤Ú˘3
Evaluation of compliance with chelation therapy in children with beta-thalassaemia major K. Papadopoulou - Legbelou1, M. Athanasiou - Metaxa2, G. Varlamis3, S. Karamperis3
¶ÂÚ›ÏË„Ë: ∆Ô Ù·ÎÙÈÎfi ÚfiÁÚ·ÌÌ· ÌÂÙ¿ÁÁÈÛ˘
Î·È ·ÔÛȉ‹ÚˆÛ˘ ¤¯ÂÈ ·˘Í‹ÛÂÈ ÙËÓ ÂÈ‚›ˆÛË ÙˆÓ
·Û¯fiÓÙˆÓ ·fi ‚-ª∞, ΢ڛˆ˜ fiÙ·Ó ˘¿Ú¯ÂÈ Î·Ï‹
Û˘ÌÌfiÚʈÛË ÛÙË ıÂڷ›·. ™ÎÔfi˜ Ù˘ ÌÂϤÙ˘
‹Ù·Ó Ó· ‰ÈÂÚ¢ÓËı› Ë Û˘ÌÌfiÚʈÛË ÛÙËÓ ·ÔÛȉ‹-
ÚˆÛË Û ¿Û¯ÔÓÙ˜ ·fi ‚-ª∞ Ô˘ ‚Ú›ÛÎÔÓÙ·È Û ٷÎÙÈÎfi ÚfiÁÚ·ÌÌ· ÌÂÙ¿ÁÁÈÛ˘-·ÔÛȉ‹ÚˆÛ˘
ÙËÓ ·Ú¯‹ Ù˘ ÓfiÛÔ˘ Î·È Ë Û˘Û¯¤ÙÈÛ‹ Ù˘ ÌÂ
‰È¿ÊÔÚÔ˘˜ ·Ú¿ÁÔÓÙ˜ fiˆ˜ Ë ËÏÈΛ·, ÙÔ Ê‡ÏÔ, Ë
¯ÚÔÓÈ΋ ‰È¿ÚÎÂÈ· Ù˘ ·ÔÛȉ‹ÚˆÛ˘, ÙÔ Û‡ÓÔÏÔ
ÙˆÓ ÌÂÙ·ÁÁ›ÛˆÓ, Ë ÙÈÌ‹ Ù˘ ·ÈÌÔÛÊ·ÈÚ›Ó˘ ÚÈÓ ÙË
ÌÂÙ¿ÁÁÈÛË Î·È Ë ÊÂÚÚÈÙ›ÓË ÙÔ˘ ÔÚÔ‡. ªÂÏÂÙ‹ıËηÓ
90 ¿Û¯ÔÓÙ˜ ·fi ÔÌfi˙˘ÁË ‚-ª∞ (48 ·ÁfiÚÈ· Î·È 42 ÎÔÚ›ÙÛÈ·) ËÏÈΛ·˜ 3-18 ¯ÚfiÓˆÓ (̤ÛË ËÏÈΛ·:
12,3±4,4 ¤ÙË), ÔÈ ÔÔ›ÔÈ ‚Ú›ÛÎÔÓÙ·Ó ÛÂ Ù·ÎÙÈÎfi
ÚfiÁÚ·ÌÌ· ÌÂÙ·ÁÁ›ÛÂˆÓ ·fi ÙËÓ ·Ú¯‹ Ù˘ ÓfiÛÔ˘
Î·È ¿Ú¯È˙·Ó ·ÔÛȉ‹ÚˆÛË Û ÙÈÌ‹ ÊÂÚÚÈÙ›Ó˘ ÂÚ›-
Ô˘ 1000 ng/ml. OÈ ¿Û¯ÔÓÙ˜ ¯ˆÚ›ÛÙËÎ·Ó Û 3
ÔÌ¿‰Â˜ ·Ó¿ÏÔÁ· Ì ÙËÓ ËÏÈΛ· (ÔÌ¿‰· ∞: <10
ÂÙÒÓ, ÔÌ¿‰· µ: 10-15 ÂÙÒÓ, ÔÌ¿‰· °: >15 ÂÙÒÓ) ηÈ
Û 3 ÔÌ¿‰Â˜ ·Ó¿ÏÔÁ· Ì ÙË Û˘ÌÌfiÚʈÛË ÛÙËÓ
·ÔÛȉ‹ÚˆÛË (1Ë ÔÌ¿‰·: η΋, 2Ë ÔÌ¿‰·: ̤ÙÚÈ·, 3Ë ÔÌ¿‰·: ηϋ). ¢È·ÈÛÙÒıËΠη΋ Û˘ÌÌfiÚʈÛË
Û 11 ·ÛıÂÓ›˜ (12%), ̤ÙÚÈ· Û˘ÌÌfiÚʈÛË Û 20 (22%) Î·È Î·Ï‹ Û˘ÌÌfiÚʈÛË Û 59 ·ÛıÂÓ›˜ (66%). ∏ ¯ÂÈÚfiÙÂÚË Û˘ÌÌfiÚʈÛË ·Ú·ÙËÚ‹ıËΠ̠ÙËÓ ·‡ÍËÛË Ù˘ ËÏÈΛ·˜, ÙˆÓ ¯ÚfiÓˆÓ ·ÔÛȉ‹ÚˆÛ˘ Î·È ÙÔ˘ ·ÚÈıÌÔ‡ ÙˆÓ ÌÂÙ·ÁÁ›ÛˆÓ, ÂÓÒ ·fi ÙÔ Ê‡ÏÔ Ê¿ÓËΠfiÙÈ Ù· ·ÁfiÚÈ· ›¯·Ó ¯ÂÈÚfiÙÂÚË
Û˘ÌÌfiÚʈÛË Û ۯ¤ÛË Ì ٷ ÎÔÚ›ÙÛÈ·. ∂›Û˘, Ë
Abstract: Regular transfusion and chelation therapy in ‚-thalassaemia have improved survival, particularly when associated with optimal compliance. The aim of this study was to investigate compliance with chelation therapy of patients with ‚-thalassaemia major who were treated with regular transfusions and chelation therapy, and the relationships between compliance and age, sex, duration of chelation therapy, number of blood transfusions and post-transfusional haemoglobin and serum ferritin levels. Ninety patients, 48 boys and 42 girls, aged 3-18 years (mean age: 12.3±4.4 years) were studied. They were all receiving regular transfusions and started chelation therapy with desferrioxamine at serum ferritin levels of approximately 1000 ng/ml. The patients were divided into three groups according to age (group A: <10 years, group B: 10-15 years, group C: >15 years). They were also classified into three groups according to compliance with chelation therapy (group I: poor, group II: moderate, group III: optimal compliance). Eleven patients (12%) exhibited poor compliance, 20 (22%) moderate and 59 (66%) optimal compliance. The poorest compliance with chelationtherapywas observedin older patients with a higher number of blood transfusions and boys showed worse compliance than girls. The non-compliant patients had a higher mean serum ferritin level. In this study the majority of patients showed good compliance with chelation therapy. The age at commencement of desferrioxamine treatment appears to be animportant determinant
1
3
1 “Papageorgiou”General Hospital, Thessaloniki
2 1st Paediatric Clinic of Aristotelion University, Thessaloniki
3 4th Paediatric Clinic of Aristotelion University, Thessaloniki
∞fi ÙËÓ ·ÚÔ‡Û· ÌÂϤÙË Û˘ÌÂÚ·›ÓÂÙ·È fiÙÈ ÔÈ ¿Û¯ÔÓÙ˜ ·fi ÔÌfi˙˘ÁË ‚-ª∞ Ô˘ ‚Ú›ÛÎÔÓÙ·È Û ٷ-
ÎÙÈÎfi ÚfiÁÚ·ÌÌ· ÌÂÙ¿ÁÁÈÛ˘ Î·È ·ÔÛȉ‹ÚˆÛ˘ ·fi ÙËÓ ·Ú¯‹ Ù˘ ÓfiÛÔ˘, ¤¯Ô˘Ó ÛÙÔ ÌÂÁ·Ï‡ÙÂÚÔ
ÔÛÔÛÙfi ηϋ Û˘ÌÌfiÚʈÛË ÛÙËÓ ·ÔÛȉ‹ÚˆÛË. ∏
¤ÁηÈÚË ¤Ó·ÚÍË Ù˘ ·ÔÛȉ‹ÚˆÛ˘ ·fi ÙËÓ ÚÒÙË
·È‰È΋ ËÏÈΛ· ‰ÂÓ ÚÔÊ˘Ï¿ÛÛÂÈ ÌfiÓÔ ·fi ÙËÓ
˘ÂÚÊfiÚÙˆÛË ÙÔ˘ ÔÚÁ·ÓÈÛÌÔ‡ Ì ۛ‰ËÚÔ, ·ÏÏ¿
Û˘Ó¿ÁÂÙ·È Î·È Î·Ï‡ÙÂÚË Û˘ÌÌfiÚʈÛË.
§¤ÍÂȘ ÎÏÂȉȿ: ÔÌfi˙˘ÁË ‚-ª∞, ·ÔÛȉ‹ÚˆÛË, Û˘Ì-
ÌfiÚʈÛË ÛÙËÓ ·ÔÛȉ‹ÚˆÛË.
∂ÈÛ·ÁˆÁ‹ ∆ËÓ ÙÂÏÂ˘Ù·›· ÂÈÎÔÛ·ÂÙ›·, Ë ıÂڷ›· Ù˘ ÔÌfi˙˘Á˘ ‚-ÌÂÛÔÁÂȷ΋˜ ·Ó·ÈÌ›·˜ (‚-ª∞) ÂÚÈÏ·Ì‚¿ÓÂÈ Ù·ÎÙÈÎfi ÚfiÁÚ·ÌÌ· ÌÂÙ·ÁÁ›ÛÂˆÓ Î·È ˘Ô‰fiÚÈ· ¯ÔÚ‹ÁËÛË Ù˘ ‰ÂÛÊÂÚÈÔÍ·Ì›Ó˘ (DFO) ÁÈ· ÙËÓ ·ÓÙÈÌÂÙÒÈÛË Ù˘ ·ÈÌÔÛȉ‹ÚˆÛ˘ (1). ∆Ô Ù·ÎÙÈÎfi ÚfiÁÚ·ÌÌ· ÌÂÙ·ÁÁ›ÛÂˆÓ ¤¯ÂÈ ÌÂÈÒÛÂÈ ÙȘ ÂÈÏÔΤ˜ Ù˘ ÌË ·ÔÙÂÏÂÛÌ·ÙÈ΋˜ ÂÚ˘ıÚÔÔ›ËÛ˘ Î·È Ù˘ ·Ó·ÈÌ›·˜, ÂÓÒ Ë ÂÊ·ÚÌÔÁ‹ Ù˘ Û˘ÛÙËÌ·ÙÈ΋˜ ·ÔÛȉ‹ÚˆÛ˘ ¤¯ÂÈ ·˘Í‹ÛÂÈ ÛËÌ·ÓÙÈο ÙÔÓ Ì¤ÛÔ fiÚÔ
ÂÈ‚›ˆÛ˘ ÙˆÓ ·Û¯fiÓÙˆÓ. ¶·Ú’ fiÏ· ·˘Ù¿, ÔÈ ÂÈ-
ÏÔΤ˜ ·fi Ù· ‰È¿ÊÔÚ· fiÚÁ·Ó·, Ô˘ ÔÊ›ÏÔÓÙ·È
ÛÙËÓ ·ÈÌÔÛȉ‹ÚˆÛË, ‰ÂÓ ¤¯Ô˘Ó ÂÍ·ÏÂÈÊı›, ΢ڛˆ˜
ÏfiÁˆ Ù˘ η΋˜ Û˘ÌÌfiÚʈÛ˘ ÛÙËÓ ·ÔÛȉ‹ÚˆÛË ‹ Ù˘ ÌË ¤ÁηÈÚ˘ ¤Ó·ÚÍ‹˜ Ù˘ (2). ∆· ·ÚÈ· fiÚÁ·Ó· Ô˘ ÚÔÛ‚¿ÏÏÔÓÙ·È ·fi ÙËÓ ÂÓ·fiıÂÛË Ûȉ‹ÚÔ˘ Â›Ó·È Ë Î·Ú‰È¿, ÙÔ ‹·Ú Î·È ÔÈ ÂÓ‰ÔÎÚÈÓ›˜ ·‰¤Ó˜ (3).
™ÎÔfi˜ Ù˘ ÌÂϤÙ˘ ‹Ù·Ó Ó· ‰ÈÂÚ¢ÓËı› Ë Û˘ÌÌfiÚʈÛË ÛÙËÓ ·ÔÛȉ‹ÚˆÛË Û ¿Û¯ÔÓÙ˜ ·fi ‚ª∞ Ô˘ ‚Ú›ÛÎÔÓÙ·È Û ٷÎÙÈÎfi ÚfiÁÚ·ÌÌ· ÌÂÙ¿ÁÁÈÛ˘-·ÔÛȉ‹ÚˆÛ˘ ·fi ÙËÓ ·Ú¯‹ Ù˘ ÓfiÛÔ˘ Î·È Ë Û˘Û¯¤ÙÈÛË Ù˘ Û˘ÌÌfiÚʈÛ˘ Ì ‰È¿ÊÔÚÔ˘˜ ·Ú¿ÁÔÓÙ˜ fiˆ˜ Ë ËÏÈΛ·, ÙÔ Ê‡ÏÔ, Ë ¯ÚÔÓÈ΋ ‰È¿ÚÎÂÈ· Ù˘ ·ÔÛȉ‹ÚˆÛ˘, ÙÔ Û‡ÓÔÏÔ ÙˆÓ ÌÔÓ¿‰ˆÓ ·›Ì·ÙÔ˜, Ë ÙÈÌ‹ Ù˘ ·ÈÌÔÛÊ·ÈÚ›Ó˘ ÚÈÓ ·fi ÙË ÌÂÙ¿ÁÁÈÛË Î·È Ë ÊÂÚÚÈÙ›ÓË ÙÔ˘ ÔÚÔ‡.
ÀÏÈÎfi Î·È Ì¤ıÔ‰ÔÈ
ªÂÏÂÙ‹ıËÎ·Ó 90 ·È‰È¿ Ô˘ ¿Û¯Ô˘Ó ·fi ÔÌfi˙˘ÁË ‚-ª∞ (48 ·ÁfiÚÈ· Î·È 42 ÎÔÚ›ÙÛÈ·) ËÏÈΛ·˜ 3-18 ¯ÚfiÓˆÓ (̤ÛË ËÏÈΛ·: 12,3±4,4 ¤ÙË). OÈ ·ÛıÂÓ›˜ ‚Ú›ÛÎÔÓÙ·Ó Û ٷÎÙÈÎfi ÚfiÁÚ·ÌÌ· ÌÂÙ¿ÁÁÈÛ˘-·ÔÛȉ‹ÚˆÛ˘ ·fi ÙËÓ ·Ú¯‹ Ù˘ ÓfiÛÔ˘, Ì ÔÈΛÏË Û˘ÌÌfiÚʈÛË ÛÙËÓ ·ÔÛȉ‹ÚˆÛË. ™Â fiÏÔ˘˜ ÙÔ˘˜ ·ÛıÂÓ›˜ Ù˘ ÌÂϤÙ˘, Ë ·ÔÛȉ‹ÚˆÛË ¤ÁÈÓ Ì ˘Ô‰fiÚÈ· ¤Á¯˘ÛË Ù˘ ‰ÂÛÊÂÚÈÔÍ·Ì›Ó˘ ÚÈÓ ·fi ÙËÓ ¤Ó·ÚÍË Ù˘ ·fi ÙÔ˘ ÛÙfiÌ·ÙÔ˜ ıÂڷ›·˜ Ì deferiprone (L1).
OÈ ¿Û¯ÔÓÙ˜ ¯ˆÚ›ÛÙËÎ·Ó Û ÙÚÂȘ ÔÌ¿‰Â˜, ·Ó¿ÏÔÁ· ÌÂ
ÙËÓ ËÏÈΛ·: Ë ÔÌ¿‰· ∞ (¡=27 ·ÛıÂÓ›˜) ÂÚÈÂÏ¿Ì‚·Ó ·ÛıÂÓ›˜ ËÏÈΛ·˜ 3-10 ¯ÚfiÓˆÓ, Ë ÔÌ¿‰· µ (¡=26 ·ÛıÂÓ›˜) ËÏÈΛ·˜
ofcompliance. The authors believe that early introduction of chelation will not only have a direct effect on iron overload, but will also lead to continued good compliance.
Key words: beta-thalassaemia major, chelation therapy, compliance.
10-15 ¯ÚfiÓˆÓ Î·È Ë ÔÌ¿‰· ° (¡=37 ·ÛıÂÓ›˜) ÂÚÈÂÏ¿Ì‚·ÓÂ
·ÛıÂÓ›˜ ËÏÈΛ·˜ 15-18 ¯ÚfiÓˆÓ. ø˜ ÚÔ˜ ÙË Û˘ÌÌfiÚʈÛË ÛÙËÓ ·ÔÛȉ‹ÚˆÛË, ÔÈ ¿Û¯ÔÓÙ˜ ¯ˆÚ›ÛÙËηÓ, ›Û˘, Û ÙÚÂȘ ÔÌ¿‰Â˜: Ë 1Ë ÔÌ¿‰· ÂÚÈÂÏ¿Ì‚·Ó ·ÛıÂÓ›˜ Ì η΋ Û˘ÌÌfiÚʈÛË (·ÔÛȉ‹ÚˆÛË <4 ÊÔÚ¤˜ ÙËÓ Â‚‰ÔÌ¿‰·), Ë 2Ë ÔÌ¿‰· ÂÚÈÂÏ¿Ì‚·Ó ·ÛıÂÓ›˜ Ì ̤ÙÚÈ· Û˘ÌÌfiÚʈÛË (·ÔÛȉ‹ÚˆÛË 4-5 ÊÔÚ¤˜ ÙËÓ Â‚‰ÔÌ¿‰·) Î·È Ë 3Ë ÔÌ¿‰· ·ÛıÂÓ›˜ Ì ηϋ Û˘ÌÌfiÚʈÛË (·ÔÛȉ‹ÚˆÛË 5-6 ÊÔÚ¤˜ ÙËÓ Â‚‰ÔÌ¿‰·). ∞fi ÙÔÓ ·ÙÔÌÈÎfi Ê¿ÎÂÏÔ ÙÔ˘ οı ·ÛıÂÓ‹, ηٷÁÚ¿ÊËÎÂ
Ô Û˘ÓÔÏÈÎfi˜ ·ÚÈıÌfi˜ ÙˆÓ ÌÂÙ·ÁÁ›ÛÂˆÓ (ÌÔÓ¿‰Â˜ ·›Ì·ÙÔ˜), Ô
̤ÛÔ˜ fiÚÔ˜ ÙˆÓ ÙÈÌÒÓ ÙˆÓ ÙÂÏÂ˘Ù·›ˆÓ 5 ¯ÚfiÓˆÓ Ù˘ ·ÈÌÔÛÊ·ÈÚ›Ó˘ Î·È Ù˘ ÊÂÚÚÈÙ›Ó˘ Î·È Ë ‰È¿ÚÎÂÈ· Ù˘ ıÂڷ›·˜
·ÔÛȉ‹ÚˆÛ˘.
∏ ÛÙ·ÙÈÛÙÈ΋ ·Ó¿Ï˘ÛË ¤ÁÈÓ Ì ÙË ‚Ô‹ıÂÈ· ËÏÂÎÙÚÔÓÈÎÔ‡ ˘ÔÏÔÁÈÛÙ‹ Î·È Ë ÂÊ·ÚÌÔÁ‹ ÙˆÓ ‚ÈÔÛÙ·ÙÈÛÙÈÎÒÓ ‰ÔÎÈÌ·ÛÈÒÓ
Ì ÙË ¯Ú‹ÛË ÙˆÓ ·Î¤ÙˆÓ SPSS for Windows ’95 Î·È StatCalc ÙÔ˘ Epilnfo 2000.
∏ ‰È·‰Èηۛ· Ù˘ ÛÙ·ÙÈÛÙÈ΋˜ ·Ó¿Ï˘Û˘ ÂÚÈÂÏ¿Ì‚·Ó ˘ÔÏÔÁÈÛÌfi ÁÈ· οı ÌÂÙ·‚ÏËÙ‹ Ù˘ ̤Û˘ ÙÈÌ‹˜ (n) Î·È Ù˘ Ù˘È΋˜ ·fiÎÏÈÛ˘ (SD). °È· ÙÔÓ ¤ÏÂÁ¯Ô ‚ÈÔÛÙ·ÙÈÛÙÈÎÒÓ ˘Ôı¤ÛˆÓ, ÂÊ·ÚÌfiÛÙËÎÂ Ë ·Ó¿Ï˘ÛË ‰È·Î‡Ì·ÓÛ˘ (Analysis of Variance-ANOVA). ∂›Û˘, ˘ÔÏÔÁ›ÛÙËÎ·Ó ÔÈ Û˘ÓÙÂÏÂÛÙ¤˜ ÌÂÙ·‚ÏËÙfiÙËÙ·˜ Î·È ÂϤÁ¯ıËÎÂ Ë ÛÙ·ÙÈÛÙÈ΋
ÛËÌ·ÓÙÈÎfiÙËÙ· ÙˆÓ Û˘ÓÙÂÏÂÛÙÒÓ r, ηٿ ÂÚ›ÙˆÛË. ∆¤ÏÔ˜, ÁÈ· ÙÔÓ ÚÔÛ‰ÈÔÚÈÛÌfi ÙˆÓ ·ÓÂÍ·Úًو˜ Û¯ÂÙÈ˙fiÌÂÓˆÓ ÌÂÙ·‚ÏËÙÒÓ Ì ÙË ÊÂÚÚÈÙ›ÓË, ÂÊ·ÚÌfiÛÙËÎ·Ó ÌÔÓ٤Ϸ ÔÏÏ·Ï‹˜ Û˘Û¯¤ÙÈÛ˘ (4).
∞ÔÙÂϤÛÌ·Ù· O ̤ÛÔ˜ fiÚÔ˜ Ù˘ ·ÈÌÔÛÊ·ÈÚ›Ó˘ ÚÈÓ ·fi ÙË ÌÂÙ¿ÁÁÈÛË, Ô Ì¤ÛÔ˜ fiÚÔ˜ Ù˘ ÊÂÚÚÈÙ›Ó˘ ÙÔ˘ ÔÚÔ‡, Ô Û˘ÓÔÏÈÎfi˜ ·ÚÈıÌfi˜ ÙˆÓ ÌÔÓ¿‰ˆÓ ·›Ì·ÙÔ˜ Î·È Ë ¯ÚÔÓÈ΋ ‰È¿ÚÎÂÈ· Ù˘ ·ÔÛȉ‹ÚˆÛ˘ Û οı ÔÌ¿‰· ·ÛıÂÓÒÓ ÂÚÈÁÚ¿ÊÔÓÙ·È ·Ó·Ï˘ÙÈο ÛÙÔÓ ¶›Ó·Î· 1. ∞fi ÙË ÌÂϤÙË Ù˘ Û˘ÌÌfiÚʈÛ˘ ÛÙËÓ ·ÔÛȉ‹ÚˆÛË, ‰È·ÈÛÙÒıËÎ·Ó Ù· ÂÍ‹˜: η΋ Û˘ÌÌfiÚʈÛË Â›¯·Ó 11 ·ÛıÂÓ›˜ (2 ·fi ÙËÓ ÔÌ¿‰· ∞, 2 ·fi ÙËÓ ÔÌ¿‰· µ Î·È 7 ·fi ÙËÓ ÔÌ¿‰· °), ̤ÙÚÈ· Û˘ÌÌfiÚʈÛË Â›¯·Ó 20 ·ÛıÂÓ›˜ (3 ·fi ÙËÓ ÔÌ¿‰· ∞, 6 ·fi
ÙËÓ ÔÌ¿‰· µ Î·È 11 ·fi ÙËÓ ÔÌ¿‰· °) Î·È Î·Ï‹ Û˘ÌÌfiÚʈÛË Â›¯·Ó 59 ·ÛıÂÓ›˜ (22 ·fi ÙËÓ ÔÌ¿‰· ∞, 18 ·fi ÙËÓ ÔÌ¿‰· µ Î·È 19 ·fi ÙËÓ ÔÌ¿‰· °) (¶›Ó·Î·˜ 2).
∞fi ÙȘ Û˘Û¯ÂÙ›ÛÂȘ ÙˆÓ ‰È·ÊfiÚˆÓ ·Ú·Ì¤ÙÚˆÓ
ˆ˜ ÚÔ˜ ÙË Û˘ÌÌfiÚʈÛË, ÚԤ΢„ fiÙÈ Ë Û˘Ì-
ÌfiÚʈÛË ÌÂÈÒÓÂÙ·È ÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈο fiÛÔ ·˘-
Í¿ÓÂÙ·È Ë ËÏÈΛ· (p<0,05), Ë ¯ÚÔÓÈ΋ ‰È¿ÚÎÂÈ· Ù˘
·ÔÛȉ‹ÚˆÛ˘ (p<0,01) Î·È Ô ·ÚÈıÌfi˜ ÙˆÓ ÌÂÙ·Á-
Á›ÛÂˆÓ (ÌÔÓ¿‰Â˜ ·›Ì·ÙÔ˜) (p<0,05) (¶›Ó·Î˜ 2 Î·È 3, ∂ÈÎfiÓ· 1).
ŸÛÔÓ ·ÊÔÚ¿ ÛÙË ÊÂÚÚÈÙ›ÓË, Ê·›ÓÂÙ·È fiÙÈ ÔÈ ¿-
Û¯ÔÓÙ˜ Ô˘ ›¯·Ó η΋ Î·È Ì¤ÙÚÈ· Û˘ÌÌfiÚʈÛË
›¯·Ó ÈÔ ˘„ËϤ˜ ÙÈ̤˜ ÊÂÚÚÈÙ›Ó˘ (ÂÚ›Ô˘ ›‰È˜
ÙÈ̤˜ ÛÙȘ ‰‡Ô ÚÒÙ˜ ÔÌ¿‰Â˜), ÂÓÒ fiÛÔÈ Â›¯·Ó η-
Ï‹ Û˘ÌÌfiÚʈÛË Â›¯·Ó ÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈο ¯·ÌË-
ÏfiÙÂÚ˜ ÙÈ̤˜ (p<0,01) (¶›Ó·Î·˜ 3 Î·È ∂ÈÎfiÓ· 2).
∏ ̤ÛË ÙÈÌ‹ Ù˘ ·ÈÌÔÛÊ·ÈÚ›Ó˘ ÚÈÓ ·fi ÙË ÌÂ-
Ù¿ÁÁÈÛË ÔÈΛÏÏÂÈ ˆ˜ ÚÔ˜ ÙË Û˘ÌÌfiÚʈÛË, Ì ‰È·-
ÊÔÚ¤˜ ÛÙ·ÙÈÛÙÈο ÌË ÛËÌ·ÓÙÈΤ˜ (p=0,48).
ŸÛÔÓ ·ÊÔÚ¿ ÛÙÔ Ê‡ÏÔ, ÛÙËÓ 1Ë ÔÌ¿‰· (Ì η-
΋ Û˘ÌÌfiÚʈÛË) ˘ÂÚÙÂÚÔ‡Ó Ù· ·ÁfiÚÈ·, ·ÏÏ¿ ÔÈ
‰È·ÊÔÚ¤˜ Â›Ó·È ÛÙ·ÙÈÛÙÈο ÌË ÛËÌ·ÓÙÈΤ˜ (p=0,58)
(¶›Ó·Î·˜ 2).
™ÙËÓ ÔÏ˘·Ú·ÁÔÓÙÈ΋ ·Ó¿Ï˘ÛË Ô˘ ¤ÁÈÓ ÁÈ·
ÙË ÌÂϤÙË Ù˘ Û˘Û¯¤ÙÈÛ˘ ÙˆÓ ÂȤ‰ˆÓ Ù˘ ÊÂÚ-
ÚÈÙ›Ó˘ Ì ÙÔ Ê‡ÏÔ, ÙËÓ ËÏÈΛ·, ÙËÓ ÙÈÌ‹ Ù˘ Hb ÚÈÓ ·fi ÙË ÌÂÙ¿ÁÁÈÛË, ÙȘ ÌÔÓ¿‰Â˜ ·›Ì·ÙÔ˜ Î·È ÙË Û˘ÌÌfiÚʈÛË ÛÙËÓ ·ÔÛȉ‹ÚˆÛË, ‰È·ÈÛÙÒıËΠfiÙÈ ˘¿Ú¯ÂÈ Û˘Û¯¤ÙÈÛË Ù˘ ÙÈÌ‹˜ Ù˘ ÊÂÚÚÈÙ›Ó˘ ÌfiÓÔ Ì ÙËÓ ·ÔÛȉ‹ÚˆÛË Î·È Ë ‰È·ÊÔÚ¿ Â›Ó·È ÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈ΋ (p<0,001).
™˘˙‹ÙËÛË
OÈ Ù·ÎÙÈΤ˜ ÌÂÙ·ÁÁ›ÛÂȘ ÛÙËÓ ÔÌfi˙˘ÁË ‚-ª∞ ηٷÛÙ¤ÏÏÔ˘Ó ÙËÓ ÂÍˆÌ˘ÂÏÈ΋ ÂÚ˘ıÚÔÔ›ËÛË Î·È
ÚÔÊ˘Ï¿ÛÛÔ˘Ó ·fi ÙËÓ ÂÌÊ¿ÓÈÛË ÛÔ‚·Ú‹˜ ·Ó·ÈÌ›·˜ (5). ŸÌˆ˜, Ë ·˘ÍË̤ÓË ÚfiÛÏË„Ë Ûȉ‹ÚÔ˘ ·fi ÙȘ Ù·ÎÙÈΤ˜ ÌÂÙ·ÁÁ›ÛÂȘ ‰È·Ù·Ú¿ÛÛÂÈ ÙÔÓ ÌÂÙ·‚ÔÏÈÛÌfi ÙÔ˘ Î·È Ô‰ËÁ› Û ÏÂfiÓ·ÛÌ· Ûȉ‹ÚÔ˘, ÙÔ ÔÔ›Ô ÂÓ·ÔÙ›ıÂÙ·È Û fiÏÔ˘˜ ÙÔ˘˜ ÈÛÙÔ‡˜ ηÈ
Ô‰ËÁ› Û ÚÔ˚Ô‡Û· ›ÓˆÛË Î·È ÏÂÈÙÔ˘ÚÁÈ΋ ·Ó¿ÚÎÂÈ· ÙˆÓ ‰È·ÊfiÚˆÓ ÔÚÁ¿ÓˆÓ (6).
∏ ¤ÁηÈÚË ¤Ó·ÚÍË Ù˘ ·ÔÛȉ‹ÚˆÛ˘ ÂÚÈÔÚ›˙ÂÈ ÙËÓ ·ÚÂÁ¯˘Ì·ÙÈ΋ ‚Ï¿‚Ë ÙˆÓ ‰È·ÊfiÚˆÓ ÔÚÁ¿ÓˆÓ, ‰ÈfiÙÈ ÚÔηÏ› ·ÚÓËÙÈÎfi ÈÛÔ˙‡ÁÈÔ Ûȉ‹ÚÔ˘ Î·È Ì›ˆÛË ÙˆÓ ·ÔıÂÌ¿ÙˆÓ
¯ÚfiÓÈ·, ˘¿Ú¯Ô˘Ó Ï›Á˜ ‚È‚ÏÈÔÁÚ·ÊÈΤ˜ ·Ó·ÊÔÚ¤˜
¶›Ó·Î·˜ 1. ∞ÈÌ·ÙÔÏÔÁÈΤ˜ ·Ú¿ÌÂÙÚÔÈ, Û˘ÓÔÏÈÎfi˜ ·ÚÈıÌfi˜ ÌÂÙ·ÁÁ›ÛÂˆÓ Î·È ¯ÚÔÓÈ΋ ‰È¿ÚÎÂÈ· Ù˘ ·ÔÛȉ‹ÚˆÛ˘ ÙˆÓ ·Û¯fiÓÙˆÓ ·fi ‚-ª∞, ·Ó¿ ÔÌ¿‰· ËÏÈΛ·˜
OÌ¿‰·º‡ÏÔ∏bºÂÚÚÈÙ›ÓËMÔÓ¿‰Â˜ ·›Ì·ÙÔ˜∞ÔÛȉ‹ÚˆÛË ∞∫ ª¤ÛË ÙÈÌ‹ (g/dl)ª¤ÛË ÙÈÌ‹ (ng/ml)(n)(Ì‹Ó˜) ∞14139,4671494,0718-2003-90 µ14129,678211585-44030-138 °20179,7632378,97105-51860-192
Hb: ·ÈÌÔÛÊ·ÈÚ›ÓË
¶›Ó·Î·˜ 2. ª¤ÛË ÙÈÌ‹ Î·È Ù˘È΋ ·fiÎÏÈÛË Ù˘ ËÏÈΛ·˜ ÙˆÓ ·Û¯fiÓÙˆÓ ·fi ‚-ª∞, Û ۯ¤ÛË Ì ÙË Û˘ÌÌfiÚʈÛË ÛÙËÓ ·ÔÛȉ‹ÚˆÛË
™˘ÌÌfiÚʈÛË∞ÚÈıÌfi˜ ·Û¯fiÓÙˆÓOÌ¿‰Â˜∏ÏÈΛ· (¯ÚfiÓÈ·) ∞Á.∫.™‡ÓÔÏÔ∞µ°ª¤ÛË ÙÈÌ‹∆˘È΋ ·fiÎÏÈÛËp
∫·Î‹741122714,553,57<0,05 ª¤ÙÚÈ·91120361113,683,48<0,05 ∫·Ï‹32275922181911,134,62<0,05
∞Á.: ·ÁfiÚÈ· ∫.: ÎÔÚ›ÙÛÈ·
¶›Ó·Î·˜ 3. ª¤ÛË ÙÈÌ‹ Î·È Ù˘È΋ ·fiÎÏÈÛË Ù˘ ¯ÚÔÓÈ΋˜ ‰È¿ÚÎÂÈ·˜ Ù˘ ·ÔÛȉ‹ÚˆÛ˘, ÙˆÓ ÌÔÓ¿‰ˆÓ ·›Ì·ÙÔ˜ Î·È Ù˘ ÙÈÌ‹˜ Ù˘ ÊÂÚÚÈÙ›Ó˘ ÙˆÓ
∞ÔÛȉ‹ÚˆÛË (Ì‹Ó˜) 134,16±47,04124,8±36,2489,64±57,72<0,01 ªÔÓ¿‰Â˜ ·›Ì·ÙÔ˜ 349±130,61304±106,65230,62±154,63<0,05 ºÂÚÚÈÙ›ÓË (ng/ml) 2409,9±1132,352488,5±823,841792,2±765,99<0,01
∫·Î‹ª¤ÙÚÈ·∫·Ï‹
HÏÈΛ· (Ì‹Ó˜)
ÃÚÔÓÈ΋ ‰È¿ÚÎÂÈ· ·ÔÛȉ‹ÚˆÛ˘ (Ì‹Ó˜)
ªÔÓ¿‰Â˜ ·›Ì·ÙÔ˜
1. ª¤Û˜ ÙÈ̤˜ Ù˘ ËÏÈΛ·˜, Ù˘ ¯ÚÔÓÈ΋˜ ‰È¿ÚÎÂÈ·˜ Ù˘
ηÈ
·›Ì·ÙÔ˜ Û ۯ¤ÛË Ì ÙË Û˘Ì-
ÛÙËÓ ·ÔÛȉ‹ÚˆÛË (η΋, ̤ÙÚÈ·, ηϋ).
Ô˘ ·Ó·Ê¤ÚÔÓÙ·È Û ·ÛıÂÓ›˜ Ô˘ ¿Ú¯ÈÛ·Ó ·ÔÛȉ‹ÚˆÛË ·fi ÙËÓ ·Ú¯‹ Ù˘ ÓfiÛÔ˘ (12,13).
™ÙËÓ ·ÚÔ‡Û· ÌÂϤÙË, fiÏÔÈ ÔÈ ¿Û¯ÔÓÙ˜ ·fi
ÔÌfi˙˘ÁË ‚-ª∞ ‚Ú›ÛÎÔÓÙ·Ó Û ٷÎÙÈÎfi ÚfiÁÚ·ÌÌ·
ÌÂÙ¿ÁÁÈÛ˘ Î·È ·ÔÛȉ‹ÚˆÛ˘ ·fi ÙËÓ ·Ú¯‹ Ù˘
ÓfiÛÔ˘ Î·È ‰È·ÈÛÙÒıËΠfiÙÈ ÙÔ ÌÂÁ·Ï‡ÙÂÚÔ ÔÛÔ-
ÛÙfi ÙˆÓ ·ÛıÂÓÒÓ Â›¯Â ηϋ ¤ˆ˜ ̤ÙÚÈ· Û˘ÌÌfiÚʈÛË ÛÙËÓ ·ÔÛȉ‹ÚˆÛË (88%). ™Â ‰‡Ô ÌÂϤÙ˜
Ô˘ ¤ÁÈÓ·Ó Û ·ÛıÂÓ›˜ Ô˘ ‰ÂÓ ¿Ú¯ÈÛ·Ó ·ÔÛȉ‹ÚˆÛË ·fi ÙËÓ ·Ú¯‹ Ù˘ ÓfiÛÔ˘, ‰È·ÈÛÙÒıËΠfiÙÈ
ÙÔ ÔÛÔÛÙfi Ù˘ Û˘ÌÌfiÚʈÛ˘ ‹Ù·Ó <70%, ÂÓÒ ÔÈ
·ÛıÂÓ›˜ Ô˘ Û˘ÌÌÔÚÊÒıËÎ·Ó Û ÌÈÎÚfiÙÂÚÔ Ô-
ÛÔÛÙfi ‹Ù·Ó Û˘Ó‹ıˆ˜ ÌÂÁ·Ï‡ÙÂÚ˘ ËÏÈΛ·˜ (2,8).
∏ ¯ÂÈÚfiÙÂÚË Û˘ÌÌfiÚʈÛË ÛÙÔ˘˜ ·ÛıÂÓ›˜ Ù˘ ÌÂϤÙ˘ Ì·˜ ·Ú·ÙËÚ‹ıËΠ̠ÙËÓ ·‡ÍËÛË Ù˘
ËÏÈΛ·˜ ηÈ, Ê˘ÛÈο, ÙÔ˘ ·ÚÈıÌÔ‡ ÙˆÓ ¯ÔÚËÁÔ‡ÌÂ-
ÓˆÓ ÌÔÓ¿‰ˆÓ ·›Ì·ÙÔ˜. ∞fi ÙË ÌÂϤÙË ÙˆÓ ËÏÈÎÈÒÓ Ê¿ÓËΠfiÙÈ ÚfiÎÂÈÙ·È ÁÈ· ·È‰È¿ Ù˘ ÂÊË‚È΋˜ ËÏÈΛ·˜, Ù· ÔÔ›· Û ÌÂÁ¿ÏÔ ‚·ıÌfi ·ÚÔ˘ÛÈ¿˙Ô˘Ó „˘¯ÔÏÔÁÈΤ˜ ·ÓÙȉڿÛÂȘ ÏfiÁˆ Ù˘ ¯ÚÔÓÈfiÙËÙ·˜ ÙÔ˘ ÓÔÛ‹Ì·ÙÔ˜ Î·È Ù˘ ¯ÚÔÓÔ‚fiÚÔ˘ ‰È·‰Èηۛ·˜ Ù˘ ·ÔÛȉ‹ÚˆÛ˘. °È· ÙÔÓ ÏfiÁÔ ·˘Ùfi, ·ÚÎÂÙ¿ ·fi ·˘Ù¿ Ù· ·È‰È¿ ¯ÚÂÈ¿ÛÙËÎ·Ó „˘¯ÔÏÔÁÈ΋ ˘ÔÛÙ‹ÚÈÍË.
∫·È ˆ˜ ÚÔ˜ ÙËÓ ËÏÈΛ·, Ù· Â˘Ú‹Ì·Ù· Ù˘ ·ÚÔ‡Û·˜ ÌÂϤÙ˘ Û˘ÌʈÓÔ‡Ó Ì ٷ Â˘Ú‹Ì·Ù· ÌÂÏÂÙÒÓ
Ô˘ ÚԷӷʤÚıËÎ·Ó (2,8). ™Â Ì›· ·Ó·‰ÚÔÌÈ΋ ÌÂ-
ϤÙË ÙˆÓ Richardson Î·È Û˘Ó (14), ‚Ú¤ıËΠ›Û˘
fiÙÈ Ë Û˘ÌÌfiÚʈÛË Â›Ó·È ·ÓÙÈÛÙÚfiʈ˜ ·Ó¿ÏÔÁË ÌÂ
ÙËÓ ËÏÈΛ· ¤Ó·Ú͢ Ù˘ ·ÔÛȉ‹ÚˆÛ˘.
∫·Î‹ ºÂÚÚÈÙ›ÓË (ng/ml) ª¤ÙÚÈ· ∫·Ï‹
∂ÈÎfiÓ· 2. ª¤Û˜ ÙÈ̤˜ Ù˘ ÊÂÚÚÈÙ›Ó˘ Û ۯ¤ÛË Ì ÙË Û˘ÌÌfiÚʈÛË ÛÙËÓ ·ÔÛȉ‹ÚˆÛË (η΋, ̤ÙÚÈ·, ηϋ).
›Û˘, fiÙÈ Ë ÔÌ¿‰· ·ÛıÂÓÒÓ ÌÂ
ÙÈ̤˜ ÊÂÚÚÈÙ›Ó˘. ∆· Â˘Ú‹Ì·Ù· Ù˘ ·ÚÔ‡Û·˜ ÌÂϤÙ˘ Û˘ÌʈÓÔ‡Ó, ›Û˘, Ì ÙË ÌÂϤÙË ÙˆÓ
Maurer Î·È Û˘Ó (8), ηıÒ˜ ›Û˘ Î·È Ì ÙË ÌÂϤÙË
ÙˆÓ ∫·ÙÙ¿ÌË Î·È Û˘Ó (15), ÛÙËÓ ÔÔ›· ‰È·ÈÛÙÒıË-
ΠÙËÓ ÙÂÏÂ˘Ù·›· 15ÂÙ›· Ì›ˆÛË ÙˆÓ ÙÈÌÒÓ Ù˘ ÊÂÚÚÈÙ›Ó˘ ÙˆÓ ·Û¯fiÓÙˆÓ ·fi ‚-ª∞ Î·È ‚ÂÏÙ›ˆÛË Ù˘
Û˘ÌÌfiÚʈÛ˘ ÛÙËÓ ·ÔÛȉ‹ÚˆÛË.
™˘ÌÂÚ·ÛÌ·ÙÈο, ·fi ÙËÓ ·ÚÔ‡Û· ÌÂϤÙË ÚÔ·ÙÂÈ fiÙÈ ÔÈ ¿Û¯ÔÓÙ˜ ·fi ÔÌfi˙˘ÁË ‚-ª∞ Ô˘ ‚Ú›ÛÎÔÓÙ·È Û ٷÎÙÈÎfi ÚfiÁÚ·ÌÌ· ÌÂÙ¿ÁÁÈÛ˘ Î·È ·ÔÛȉ‹ÚˆÛ˘ ·fi ÙËÓ ·Ú¯‹ Ù˘ ÓfiÛÔ˘, ¤¯Ô˘Ó
ÛÙÔ ÌÂÁ·Ï‡ÙÂÚÔ ÔÛÔÛÙfi Û¯ÂÙÈο ηϋ Û˘ÌÌfiÚʈÛË ÛÙË ıÂڷ›· ·ÔÛȉ‹ÚˆÛ˘.
∂ÎÙfi˜ fï˜ ·fi ÙË Û˘ÌÌfiÚʈÛË, ÛËÌ·ÓÙÈÎfi
ÚfiÏÔ Ê·›ÓÂÙ·È Ó· ·›˙ÂÈ Î·È Ë ËÏÈΛ· ¤Ó·Ú͢ Ù˘ ·ÔÛȉ‹ÚˆÛ˘. ∏ ¤Ó·ÚÍ‹ Ù˘ ·fi ÙËÓ ÚÒÙË ·È‰È΋ ËÏÈΛ· ‰ÂÓ ÚÔÊ˘Ï¿ÛÛÂÈ ÌfiÓÔ ·fi ÙËÓ ˘ÂÚÊfiÚÙˆÛË ÙÔ˘ ÔÚÁ·ÓÈÛÌÔ‡ Ì ۛ‰ËÚÔ, ·ÏÏ¿ Û˘Ó¿ÁÂÙ·È Î·È Î·Ï‡ÙÂÚË Û˘ÌÌfiÚʈÛË.
µÈ‚ÏÈÔÁÚ·Ê›·
1. Vecchio C, Derchi G. Management of cardiac complications in patients with thalassemia major. Semin Hematol 1995;32:288-296.
2. Olivieri NF, Brittenham GM. Iron-chelating therapy and the treatment of thalassemia. Blood 1997;89:739-761.
3. µuja LM, Roberts WC. Iron in the heart. Etiology and clinical significance. Am J Med 1971;51:209-221.
4. Armitage P, Berry G. Statistical methods in medical research. 2nd ed. Oxford: Blackwell Scientific Publications; 1989.
5. Fosburg MT, Nathan DG. Treatment of Cooley’s anemia. Blood 1990;76:435-444.
ŸÛÔÓ ·ÊÔÚ¿ ÛÙÔ Ê‡ÏÔ ÙˆÓ ·ÛıÂÓÒÓ Ù˘ ·ÚÔ‡Û·˜ ÌÂϤÙ˘, ·Ú·ÙËÚ‹ıËΠfiÙÈ Ù· ·ÁfiÚÈ· ¤¯Ô˘Ó ¯ÂÈÚfiÙÂÚË Û˘ÌÌfiÚʈÛË ·fi Ù· ÎÔÚ›ÙÛÈ·. ∫·È ÛÙËÓ ÂÚ›ÙˆÛË ·˘Ù‹, ÂÚfiÎÂÈÙÔ ÁÈ· ·ÁfiÚÈ· ÂÊË‚È΋˜ ËÏÈΛ·˜, Ù· ÔÔ›· Èı·ÓfiÓ ÏfiÁˆ ÔÚÌÔÓÈ-
6. Giardina PJ, Grady RW. Chelation therapy in betathalassemia: the benefits and limitations of desferrioxamine. Semin Hematol 1995;32:304-312.
7. Weatherall DJ, Clegg JB. The thalassaemic syndromes. 3rd ed. Oxford: Blackwell Scientific Publications; 1981.
8. Maurer HS, Lloyd-Still JD, Ingrisano C, Gonzalez-Crussi F, Honig GR. A prospective evaluation of iron chelation therapy in children with severe beta-thalassemia. A six-year study. Am J Dis Child 1988;142:287-292.
9. Giardina PJ, Grady RW, Ehlers KH, Burstein S, Graziano JH, Markenson AL et al. Current therapy of Cooley’s anemia. A decade of experience with subcutaneous desferrioxamine. Ann NY Acad Sci 1990;612:275-285.
10. Olivieri NF, Nathan DG, MacMillan JH, Wayne AS, Liu PP, McGee A et al. Survival in medically treated patients with homozygous beta-thalassemia. N Engl J Med 1994;331:574-578.
11. Cohen A, Martin M, Schwartz E. Response to long-term deferoxamine therapy in thalassemia. J Pediatr 1981;99:689-694.
12. Borgna-Pignatti C, Piga A, Rugolotto S, De Stefano P, Di Palma AM, Gamberini R et al. Survival and disease complications in thalassemia major. Bone Marrow Transplant 1997;19 (Suppl 2):S16-S17.
13. Ladis V, Papadopoulou A, Athanassaki C, Palamidou F,
Kostaridou S, Berdousi E et al. Long term survival and causes of death in patients with thalassemia under conventional treatment. Bone Marrow Transplant 1997;19 (Suppl 2):S4-S6.
14. Richardson ME, Matthews RN, Alison JF, Menahem S, Mitvalsky J, Byrt E et al. Prevention of heart disease by subcutaneous desferrioxamine in patients with thalassaemia major. Aust NZ J Med 1993;23:656-661.
15. Kattamis AC, Dinopoulos A, Ladis V, Athanassaki K, Palamidou F. Changing pattern in ferritin levels among transfused patients with thalassemia on desferrioxamine in a period of 15 years. Proceedings of the 7th International Conference of thalassemia and haemoglobinopathies. Bangkok Thailand; 1999 May 31-June 4; p. 272.
∏ÌÂÚÔÌËÓ›· ˘Ô‚ÔÏ‹˜: 20-09-2002
∏ÌÂÚÔÌËÓ›· ¤ÁÎÚÈÛ˘: 07-02-2003
¢È‡ı˘ÓÛË ·ÏÏËÏÔÁÚ·Ê›·˜: ∫˘Úȷ΋ ¶··‰ÔÔ‡ÏÔ˘-§ÂÁ̤ÏÔ˘
º›Ï˘ÚÔ, ∆.∫. 570 10, £ÂÛÛ·ÏÔÓ›ÎË
E-mail: legbelos@hol.gr
∂¡¢π∞º∂ƒOÀ™∞ ¶∂ƒπ¶∆ø™∏CASE REPORT
™‡Ó‰ÚÔÌÔ Nail-Patella (ÔÛÙÂÔ-ÔÓ˘¯Ô‰˘ÛÙÚÔÊ›·). ¶ÂÚÈÁÚ·Ê‹
π. π. πÁÓ·ÙÈ¿‰Ë˜, ª. ∑. °Ô˘‰ÂÛ›‰Ô˘, ∞. §. ¶··‰ÔÔ‡ÏÔ˘, ∫. ∆ÛÔ˘Ì¿Î·˜
Nail-Patella syndrome. A case report
J. J. Ignatiadis, M. Z. Goudesidou, A. L. Papadopoulou, C. Tsoumakas
¶ÂÚ›ÏË„Ë: ∆Ô Û‡Ó‰ÚÔÌÔ Nail-Patella (NPS) Û˘Ó‰˘¿˙ÂÈ ·Ô˘Û›· ÂÈÁÔÓ·Ù›‰ˆÓ, ÔÓ˘¯Ô‰˘ÛÙÚÔÊ›·,
Ï·ÁÒÓȘ ÂÍÔÛÙÒÛÂȘ Î·È Û˘ÁÁÂÓ‹ Û‡Áη̄Ë
·ÁÎÒÓˆÓ. ™˘¯Ó¿ Û˘Ó˘¿Ú¯ÂÈ ÓÂÊÚÔ¿ıÂÈ· ÌÂ Û˘Á-
ÁÂÓ›˜ ‰È·Ì·Úٛ˜ Ô˘ÚÔÔÈËÙÈÎÔ‡, ÔÊı·ÏÌÈΤ˜ ·Óˆ-
̷ϛ˜ Î·È ÓfiÛÔ˜Goodpasture. ∫ÏËÚÔÓÔÌÂ›Ù·È ÌÂ
·˘ÙÔۈ̷ÙÈÎfi ÂÈÎÚ·ÙÔ‡ÓÙ· ¯·Ú·ÎÙ‹Ú· Î·È ÔÊ›-
ÏÂÙ·È Û ÌÂÙ¿ÏÏ·ÍË ÙÔ˘ ÁÔÓȉ›Ô˘ LMX1B Ô˘ ¤¯ÂÈ
¯·ÚÙÔÁÚ·ÊËı› ÚfiÛÊ·Ù· ÛÙÔ ¯ÚˆÌfiۈ̷ 9 ÛÙËÓ
Ù·ÈÓ›· q34.1. ∫ÔÚ›ÙÛÈ ËÏÈΛ·˜ 4 ¯ÚfiÓˆÓ ÚÔÛ‹ÏıÂ
ÁÈ· ¤ÏÂÁ¯Ô ÏfiÁˆ ÔÓ˘¯Ô‰˘ÛÙÚÔÊ›·˜. ™ÙËÓ ÎÏÈÓÈ΋
ÂͤٷÛË Î·È ÛÙÔÓ ·ÂÈÎÔÓÈÛÙÈÎfi ¤ÏÂÁ¯Ô Ô˘ ·ÎÔ-
ÏÔ‡ıËÛÂ, ÏËÓ Ù˘ ÔÓ˘¯Ô‰˘ÛÙÚÔÊ›·˜, ‰È·ÈÛÙÒıË-
Î·Ó ÂÈϤÔÓ ·Ô˘Û›· ÂÈÁÔÓ·Ù›‰ˆÓ, Ï·ÁfiÓȘ ÂÍÔ-
ÛÙÒÛÂȘ Î·È Û‡ÁÎ·Ì„Ë ÙˆÓ ·ÁÎÒÓˆÓ. ∆Ô ·ÙÔÌÈÎfi
·Ó·ÌÓËÛÙÈÎfi ‹Ù·Ó ÂχıÂÚÔ, ÂÓÒ ÛÙÔ ÔÈÎÔÁÂÓÂÈ·Îfi
ÈÛÙÔÚÈÎfi, Ë ÌËÙ¤Ú· Ù˘ ·ÛıÂÓÔ‡˜ ›¯Â ˘Ô‚ÏËı›
Û ¤̂·ÛË Û ËÏÈΛ· 17 ¯ÚfiÓˆÓ ÏfiÁˆ Û‡ÁηÌ-
„˘ ·ÁÎÒÓˆÓ. O ·‰Úfi˜ ‚ÈÔ¯ËÌÈÎfi˜, Ô ÂÓ‰Âϯ‹˜
¤ÏÂÁ¯Ô˜ Ù˘ ÓÂÊÚÈ΋˜ ÏÂÈÙÔ˘ÚÁ›·˜ Î·È ÙÔ˘ ÌÂÙ·‚Ô-
ÏÈÛÌÔ‡ ÙÔ˘ ·Û‚ÂÛÙ›Ô˘ Î·È Ô ¤ÏÂÁ¯Ô˜ ÁÈ· Û˘ÛÙËÌ·-
ÙÈ΋ ÓfiÛÔ ‹Ù·Ó ·ÚÓËÙÈÎÔ›. ∏ ·ÛıÂÓ‹˜ ˘Ô‚Ï‹ıËÎÂ
Û ¯ÂÈÚÔ˘ÚÁÈ΋ ¤̂·ÛË ÁÈ· ·ÔηٿÛÙ·ÛË ÙˆÓ
·ÁÎÒÓˆÓ Ì ÈηÓÔÔÈËÙÈο ·ÔÙÂϤÛÌ·Ù·. ∏ ·Ô˘-
Û›· ÂÈÁÔÓ·Ù›‰ˆÓ ‰ÂÓ ‰ËÌÈÔ˘ÚÁ› ÚÔ‚Ï‹Ì·Ù· ·Ó·-
ËÚ›·˜. ∏ ¤ÁηÈÚË ‰È¿ÁÓˆÛË Î·È Ë ¯ÂÈÚÔ˘ÚÁÈ΋
·ÔηٿÛÙ·ÛË ÚÔÛʤÚÔ˘Ó ÛÙÔ˘˜ ·ÛıÂÓ›˜ ۯ‰fiÓ Ê˘ÛÈÔÏÔÁÈ΋ ˙ˆ‹. ∞·ÈÙ›ٷÈ, fï˜, Û˘¯Ófi˜
¤ÏÂÁ¯Ô˜ ÁÈ· ÙÔ ÂӉ¯fiÌÂÓÔ Û˘ÛÙËÌ·ÙÈÎÒÓ ÂΉËÏÒÛˆÓ. O ÚÔÁÂÓÓËÙÈÎfi˜ ¤ÏÂÁ¯Ô˜ ÙÔ˘ Û˘Ó‰ÚfiÌÔ˘ Â›Ó·È ÂÊÈÎÙfi˜, Ë ÙÂÎÓÔÔ›ËÛË fï˜ ·Ôı·ÚÚ‡ÓÂÙ·È Î˘Ú›ˆ˜ ÁÈ· ÙÔÓ Î›Ó‰˘ÓÔ ÛÔ‚·Ú‹˜ ÓÂÊÚÈ΋˜ ‚Ï¿‚˘.
§¤ÍÂȘ ÎÏÂȉȿ: Nail-Patella, Turner-Kieser, Û‡ÁÎ·Ì„Ë ·ÁÎÒÓˆÓ, ÔÓ˘¯Ô‰˘ÛÏ·Û›·.
Abstract: Nail-Patella syndrome (NPS) is a rare autosomal dominant disorder associated with onychodysplasia, antecubital pterygium, hypoplasia or absent patellae, and iliac horns. Nephropathy is often associated with genetic anomalies of the urinary tract, ophthalmic disorders and Goodpasture syndrome. It is the result of a mutation in LMX1B gene, recently mapped in the 9q34.1 chromosomal locus. A 4-year old girl presented with onychodysplasia which on clinical and radiological examination was associated with bilateral antecubital pterygium and absence of patellae. Her previous medical history was insignificant but her mother had a history of antecubital pterygium for which she was operated, during adolescence. The girl’s renal and liver function, and her calcium metabolism were normal. No laboratory evidence of systematic disease was found. She was operated with satisfactory results. Absence of patellae does not cause any disability. The early diagnosis and surgical correction helps patients lead a normal life, nevertheless, frequent tests for systematic complications are needed. Prenatal diagnosis is possible today but childbearing is discouraged mainly because of renal complications.
Key words: Nail-Patella, Turner-Kieser, antecubital pterygium, onychodysplasia.
¶·È‰È·ÙÚÈÎfi ∆Ì‹Ì·, °ÂÓÈÎfi ¡ÔÛÔÎÔÌÂ›Ô ∫∞∆, ∞ÙÙÈ΋Pediatric Department, KAT General Hospital, Attiki
™˘ÓÙÔÌÔÁڷʛ˜
¡PS™‡Ó‰ÚÔÌÔ ¡ail-Patella
BM™µ·ÛÈ΋ ÌÂÌ‚Ú¿ÓË ÛÂÈÚ¿Ì·ÙÔ˜
∂ÈÛ·ÁˆÁ‹
∆Ô Û‡Ó‰ÚÔÌÔ Nail-Patella (NPS) ‹ “TurnerKieser”, ÙÔ ÔÔ›Ô ¯·Ú·ÎÙËÚ›˙ÂÙ·È ·fi ·ÚıÚÔ-ÔÓ˘¯Ô-ÔÛÙÂÔ‰˘ÛÏ·Û›·, Â›Ó·È ÎÏËÚÔÓÔÌÔ‡ÌÂÓÔ ÓfiÛËÌ·. ™˘Ó‰˘¿˙ÂÈ ÔÓ˘¯Ô‰˘ÛÙÚÔÊ›·, ȉ›ˆ˜ ÛÙÔ˘˜ ·ÓÙ›¯ÂÈÚ˜ (·Ï·Û›·, ηٷÎÂÚÌ·ÙÈÛÌfi, ·Ô¯ÚˆÌ·ÙÈÛÌfi) (90%), Û˘ÁÁÂÓ‹ ·Ô˘Û›· ÂÈÁÔÓ·Ù›‰ˆÓ(60%), Ï·ÁfiÓȘ ÎÂÚ·ÙfiÌÔÚʘ ÂÍÔÛÙÒÛÂȘ (80%) Î·È Û˘ÁÁÂÓ‹ Û‡ÁÎ·Ì„Ë ·ÁÎÒÓ· (antecubital pterygium) (1-3). ™˘¯Ó¿ Û˘Ó˘¿Ú¯ÂÈ ÓÂÊÚÔ¿ıÂÈ·, Û˘ÁÁÂÓ›˜ ·ÓˆÌ·Ï›Â˜ ÙÔ˘ Ô˘ÚÔÔÈËÙÈÎÔ‡ Û˘ÛÙ‹Ì·ÙÔ˜, ÔÊı·ÏÌÈΤ˜ ·ÓˆÌ·Ï›Â˜ Î·È Û‡Ó‰ÚÔÌÔ Goodpasture (4-8).
O Little, ÙÔ 1897 (9), ·Ú’ fiÏÔ Ô˘ ·ÚÔ˘Û›·Û ÌfiÓÔ ÙȘ ·ÓˆÌ·Ï›Â˜ Ù˘ ÂÈÁÔÓ·Ù›‰·˜, ıˆÚÂ›Ù·È Ô
ÚÒÙÔ˜ Ô˘ ÂÚȤÁÚ·„ ÙÔ Û‡Ó‰ÚÔÌÔ, ÂÓÒ Û˘ÓÔÏÈο ̤¯ÚÈ Û‹ÌÂÚ· ¤¯Ô˘Ó ·Ó·ÊÂÚı› ÂÚ›Ô˘ 400 ÂÚÈÙÒÛÂȘ. ¶ÚfiÎÂÈÙ·È ÁÈ· Û˘ÁÁÂÓ¤˜ ÓfiÛËÌ·, ÎÏËÚÔÓÔÌÔ‡ÌÂÓÔ Ì ·˘ÙÔۈ̷ÙÈÎfi ÂÈÎÚ·ÙÔ‡ÓÙ· ¯·Ú·ÎÙ‹Ú·, ÔÊÂÈÏfiÌÂÓÔ Û ÌÂÙ¿ÏÏ·ÍË ÙÔ˘ ÁÔÓȉ›Ô˘
LMX1B ÛÙÔ ¯ÚˆÌfiۈ̷ 9q34.1 (10,11). ¶ÚfiÛÊ·Ù·, ‰È·ÈÛÙÒıËΠ¿ÏÏË ÌÂÙ¿ÏÏ·ÍË Û ‰È·ÊÔÚÂÙÈÎfi ÁÔÓȉ›Ô ˆ˜ ˘Â‡ı˘ÓË ÁÈ· ÙË ÓÂÊÚÔ·ıËÙÈ΋ ÌÔÚÊ‹ Ù˘ ÓfiÛÔ˘ (12).
¶ÂÚÈÁÚ·Ê‹ ÂÚ›ÙˆÛ˘
∫ÔÚ›ÙÛÈ ËÏÈΛ·˜ 4 ÂÙÒÓ, ÔÌ·ÎÈ΋˜ ηٷÁˆÁ‹˜, ÚÔÛ‹Ïı ÛÙ· ∂͈ÙÂÚÈο π·ÙÚ›· ÙÔ˘ ¶·È‰È·ÙÚÈÎÔ‡ ∆Ì‹Ì·ÙÔ˜ ÙÔ˘ ¡ÔÛÔÎÔÌ›Ԣ ∫∞∆ ÏfiÁˆ ÔÓ˘¯Ô‰˘ÛÙÚÔÊ›·˜. ¶ÚfiÎÂÈÙ·È ÁÈ· ÙÔ ÌÔÓ·‰ÈÎfi ·È‰› Ê·ÈÓÔÙ˘Èο ˘ÁÈÒÓ ÁÔÓ¤ˆÓ. ∏ ·ËÛË, Ô ÙÔÎÂÙfi˜ Î·È Ë ÂÚÈÁÂÓÓËÙÈ΋ ÂÚ›Ô‰Ô˜ ‹Ù·Ó Ê˘ÛÈÔÏÔÁÈο. ∆Ô ·ÙÔÌÈÎfi ÈÛÙÔÚÈÎfi ‹Ù·Ó ÂχıÂÚÔ. ∞fi ÙÔ ÔÈÎÔÁÂÓÂÈ·Îfi
ÈÛÙÔÚÈÎfi ·Ó·Ê¤ÚÂÙ·È fiÙÈ Ë ÌËÙ¤Ú· ·ÚÔ˘Û›·˙ ۇ-
∂ÈÎfiÓ· 1. OÓ˘¯Ô‰˘ÛÏ·Û›·.
ÁÎ·Ì„Ë ·ÁÎÒÓˆÓ, ÁÈ· ÙËÓ ÔÔ›· ¯ÂÈÚÔ˘ÚÁ‹ıËΠÛÂ
ËÏÈΛ· 17 ÂÙÒÓ, ·Ô˘Û›· ÂÈÁÔÓ·Ù›‰ˆÓ ¿Ìʈ ηÈ
ÔÓ˘¯Ô‰˘ÛÙÚÔÊ›·. ∏ ·‰ÂÏÊ‹ Ù˘ ÌËÙ¤Ú·˜ ·ÚÔ˘-
Û›·˙ ÙËÓ ›‰È· ÎÏÈÓÈ΋ ÂÈÎfiÓ· Î·È ˘Ô‚Ï‹ıËΠÛÙËÓ
¯ÂÈÚÔ˘ÚÁÈ΋ ·ÔηٿÛÙ·ÛË. ¢ÂÓ ·Ó·Ê¤ÚÂÙ·È
ÓÂÊÚÈ΋ ÓfiÛÔ˜ ÛÙËÓ ÔÈÎÔÁ¤ÓÂÈ·.
™ÙËÓ ·ÓÙÈÎÂÈÌÂÓÈ΋ ÂͤٷÛË, Ë ·ÛıÂÓ‹˜ ·ÚÔ˘Û›·˙ ÌÂÚÈ΋ ·Ï·Û›· Î·È Î·Ù·ÎÂÚÌ·ÙÈÛÌfi ÙˆÓ ÔÓ‡¯ˆÓ Î·È ÛÙÔ˘˜ ‰‡Ô ·ÓÙ›¯ÂÈÚ˜ (∂ÈÎfiÓ· 1) Î·È Û‡ÁÎ·Ì„Ë ÙˆÓ ·ÁÎÒÓˆÓ Î·Ù¿ 90Ô Ì ·‰˘Ó·Ì›· ¤ÎÙ·Û˘ (∂ÈÎfiÓ· 2). ∂›¯Â Ê˘ÛÈÔÏÔÁÈ΋ ÎÈÓËÙÈ΋ ÂͤÏÈÍË
Î·È Ô ¤ÏÂÁ¯Ô˜ ÙˆÓ ˘fiÏÔÈˆÓ Û˘ÛÙËÌ¿ÙˆÓ ‹Ù·Ó
Ê˘ÛÈÔÏÔÁÈÎfi˜. ÀÔ‚Ï‹ıËΠ۠ϋÚË ·ÎÙÈÓÔÏÔÁÈÎfi ¤ÏÂÁ¯Ô, ÛÙÔÓ ÔÔ›Ô ‰È·ÈÛÙÒıËÎ·Ó ÂÈϤÔÓ ˘ÔÏ·Û›· Î·È ˘ÂÍ¿ÚıÚËÌ· ÎÂÊ·ÏÒÓ ÎÂÚΛ‰ˆÓ (∂ÈÎfiÓ· 3), Ï‹Ú˘ ·Ô˘Û›· ÂÈÁÔÓ·Ù›‰ˆÓ (∂ÈÎfiÓ· 4) Î·È Ï·ÁfiÓȘ ÂÍÔÛÙÒÛÂȘ. O ·‰Úfi˜ ‚ÈÔ¯ËÌÈÎfi˜ Î·È Ô ÂÓ‰Âϯ‹˜ ¤ÏÂÁ¯Ô˜ Ù˘ ÓÂÊÚÈ΋˜ ÏÂÈÙÔ˘ÚÁ›·˜ Î·È ÙÔ˘ ÌÂÙ·‚ÔÏÈÛÌÔ‡ ÙÔ˘ ·Û‚ÂÛÙ›Ô˘, ηıÒ˜ Î·È Ô ¤ÏÂÁ¯Ô˜ ÁÈ· Û˘ÛÙËÌ·ÙÈÎfi ÓfiÛËÌ·, ‹Ù·Ó ·ÚÓËÙÈÎÔ›. ™Â ËÏÈΛ· ÂÓfi˜ ¤ÙÔ˘˜, Ë ·ÛıÂÓ‹˜ ›¯Â ¿ÏÈ ÂÏÂÁ¯ı› Û ¡ÔÛÔÎÔÌÂ›Ô ¶·›‰ˆÓ, fiÔ˘ Î·È ÙfiÙ ·ÔÎÏ›ÛÙËΠÓÂÊÚÈ΋, ηډÈÔÏÔÁÈ΋ ‹ ¿ÏÏË Û˘ÛÙËÌ·ÙÈ΋ ¿ıËÛË.
∏ ÎÏÈÓÈ΋ Î·È ·ÂÈÎÔÓÈÛÙÈ΋ ÂÈÎfiÓ· Ù˘ ·ÛıÂÓÔ‡˜ ¤ıÂÛ ÙË ‰È¿ÁÓˆÛË ÙÔ˘ Û˘Ó‰ÚfiÌÔ˘ NailPatella. °ÂÓÂÙÈÎfi˜ ¤ÏÂÁ¯Ô˜ ‰ÂÓ ¤ÁÈÓ ÏfiÁˆ ¿ÚÓËÛ˘
ÙˆÓ ÁÔÓ¤ˆÓ.
∞ÊÔ‡ Ù¤ıËΠÚÔÂÁ¯ÂÈÚËÙÈο ‰˘Ó·ÌÈÎfi˜ Ó¿ÚıËη˜ ¤ÎÙ·Û˘ Ù‡Ô˘ Orthotec ÁÈ· 2 ÂÚ›Ô˘ Ì‹Ó˜ (∂ÈÎfiÓ· 5), ¯ÂÈÚÔ˘ÚÁ‹ıËΠÛÙËÓ ÚfiÛıÈ· ÂÈÊ¿ÓÂÈ·
ÙÔ˘ ·ÚÈÛÙÂÚÔ‡ ·ÁÎÒÓ· Ì ÙÔÌ‹ Ù‡Ô˘ “Z” Î·È ¤ÁÈÓÂ
ÂÈÌ‹Î˘ÓÛË Î·È ·ÂÏ¢ı¤ÚˆÛË ÙˆÓ ÙÂÓfiÓÙˆÓ ÙˆÓ
ηÌÙ‹ÚˆÓ ÙÔ˘ ·ÁÎÒÓ·. ªÂÙÂÁ¯ÂÈÚËÙÈο, ÙÔÔıÂÙ‹ıËΠÂÎ Ó¤Ô˘ Ô ›‰ÈÔ˜ ‰˘Ó·ÌÈÎfi˜ Ó¿ÚıËη˜ ÁÈ· 6 Ì‹Ó˜ Î·È ¤ÁÈÓ ÚÔԉ¢ÙÈ΋ ¤ÎÙ·ÛË ÙÔ˘ ·ÁÎÒÓ· ÛÙȘ 165-170 ÌÔ›Ú˜ (∂ÈÎfiÓ· 6). ªÂÙ¿ ÙËÓ ·Ê·›ÚÂÛË ÙÔ˘ Ó¿ÚıËη, Ë ¤ÎÙ·ÛË ÂÚÈÔÚ›ÛÙËΠηٿ 15-
∂ÈÎfiÓ· 2. ™˘ÁÁÂÓ‹˜ Û‡ÁÎ·Ì„Ë ·ÁÎÒÓ·.
∂ÈÎfiÓ· 3. ÀÔÏ·ÛÙÈΤ˜ ÎÂʷϤ˜ ÎÂÚΛ‰ˆÓ.
∂ÈÎfiÓ· 5. ∂Ê·ÚÌÔÁ‹ ‰˘Ó·ÌÈÎÔ‡ Ó¿ÚıËη.
20 ÌÔ›Ú˜. ∏ ·Ú·ÎÔÏÔ‡ıËÛË Ù˘ ·ÛıÂÓÔ‡˜ Û˘ÓÂ-
¯›ÛÙËΠÁÈ· ÌÂÚÈÎÔ‡˜ Ì‹Ó˜ ·ÎfiÌ· Î·È ÂȂ‚·ÈÒıËÎÂ Ë ÛÙ·ıÂÚÔÔ›ËÛË Ù˘ ¤ÎÙ·Û˘.
™˘˙‹ÙËÛË
∆o NPS Â›Ó·È Û¿ÓÈÔ ÁÂÓÂÙÈÎfi ÓfiÛËÌ· Ô˘ ÂΉË-
ÏÒÓÂÙ·È ¿ÓÙ· Ì ·ÓˆÌ·Ï›Â˜ ·fi ÙÔ ÛÎÂÏÂÙÈÎfi Û‡ÛÙËÌ· Î·È ÂÓ›ÔÙÂ Û˘Ó‰˘¿˙ÂÙ·È Ì ÓÂÊÚÈ΋ ÓfiÛÔ, ÔÊı·ÏÌÈΤ˜ ·ÓˆÌ·Ï›Â˜ Î·È Û‡Ó‰ÚÔÌÔ Goodpasture.
OÈ ÛÎÂÏÂÙÈΤ˜ ·ÓˆÌ·Ï›Â˜ ÂΉËÏÒÓÔÓÙ·È Î˘Ú›ˆ˜ ÛÙȘ ÂÈÁÔÓ·Ù›‰Â˜ (·Ô˘Û›· ‹ ˘ÔÏ·Û›·, knockknee), ÛÙÔ˘˜ ·ÁÎÒÓ˜ (·Ï·Û›· ‹ ˘ÔÏ·Û›·, Û‡Áη„Ë) Î·È ÛÙ· Ï·ÁfiÓÈ· ÔÛÙ¿ (ÂÍÔÛÙÒÛÂȘ). ¶·Ú·ÙËÚ›ٷÈ, ›Û˘, ÔÓ˘¯Ô‰˘ÛÏ·Û›· (·Ô˘Û›·, ·Ô¯ÚˆÌ·ÙÈÛÌfi˜, ÎÔÈÏÔÓ˘¯›·). OÈ ‚Ï¿‚˜ Â›Ó·È Û˘Ó‹ıˆ˜ Û˘ÌÌÂÙÚÈΤ˜. ™˘¯Ó¿ Û˘Ó˘¿Ú¯Ô˘Ó ·˘¯ÂÓÈ΋ ÏÂ˘Ú¿, ˘ÔÏ·Û›· ¤Íˆ ÌËÚÈ·›ˆÓ ÎÔÓ‰‡ÏˆÓ ‹ ÎÔÓ‰‡ÏˆÓ ‚Ú·¯ÈÔÓ›Ô˘ (Capitelum) ‹ ÎÂÊ·Ï‹˜ ÎÂÚΛ‰Ô˜, ÎÂÊ·Ï‹˜ ÂÚfiÓ˘, ·Ï·Û›Â˜ Ì˘ÒÓ (΢ڛˆ˜ ÙÔ˘ Ì›˙ÔÓÔ˜ ıˆÚ·ÎÈÎÔ‡) Î·È Û˘ÁÁÂÓ‹˜ ·Ô˘Û›· ÔÓ˘¯ÔÊfi-
∂ÈÎfiÓ· 4. ∞Ô˘Û›· ÂÈÁÔÓ·Ù›‰ˆÓ.
∂ÈÎfiÓ· 6. ∂ÈÌ‹Î˘ÓÛË Î·È ·ÂÏ¢ı¤ÚˆÛË ÙÔ˘ ·ÁÎÒÓ· (ÙÔÌ‹ Ù‡Ô˘ ∑).
ÚˆÓ Ê·Ï¿ÁÁˆÓ (13). ∏ ·Ô˘Û›· ÙˆÓ ÂÈÁÔÓ·Ù›‰ˆÓ ‰ÂÓ ÂËÚ¿˙ÂÈ ÙË ÏÂÈÙÔ˘ÚÁÈ΋ ÈηÓfiÙËÙ· ÙÔ˘ ·ÙfiÌÔ˘, ‰ÂÓ ÂÈÙÚ¤ÂÈ, fï˜, ÙËÓ ¤ÓÙÔÓË ¿ÛÎËÛË Î·È È‰È·›ÙÂÚ· ÙÔÓ ÚˆÙ·ıÏËÙÈÛÌfi. ŸÌˆ˜, Û˘¯Ó¿ ÂÈϤÎÂÙ·È Ì ÔÛÙÂÔ·ÚıÚ›Ùȉ·, Ë ÔÔ›· ÌÔÚ› Ó· Â›Ó·È ‹È· Î·È Ó· ·ÓÙÈÌÂÙˆ›˙ÂÙ·È Û˘ÓÙËÚËÙÈο, ÌÔÚ› fï˜ Û¿ÓÈ· Ó· ¯ÚÂÈ·ÛÙ›·ÚıÚÔÏ·ÛÙÈ΋ ·ÔηٿÛÙ·ÛË (14). ∏ ·ÚÔ˘Û›· ÙˆÓ ˘fiÏÔÈˆÓ ÛÎÂÏÂÙÈÎÒÓ ·ÓˆÌ·ÏÈÒÓ ‰ËÌÈÔ˘ÚÁ› ÂÚÈÔÚÈÛÌfi Ù˘ ÎÈÓËÙÈÎfiÙËÙ·˜ ηÈ, ÌÂÚÈΤ˜ ÊÔÚ¤˜, ÛÔ‚·Úfi ·ÈÛıËÙÈÎfi Úfi‚ÏËÌ·. ∏ ·ÛıÂÓ‹˜ Ô˘ ÂÚÈÁÚ¿ÊÂÙ·È ·ÚÔ˘Û›·˙Â, ÂÎÙfi˜ ·fi ÙËÓ ÔÓ˘¯Ô‰˘ÛÏ·Û›· (ÁÈ· ÙËÓ ÔÔ›· Î·È ÚÔÛ‹Ïı ÛÙÔ ÓÔÛÔÎÔÌ›Ô), ÙȘ ÂÍ‹˜ ÛÎÂÏÂÙÈΤ˜ ·ÓˆÌ·Ï›Â˜: Û‡Áη„Ë ·ÁÎÒÓˆÓ, ·Ô˘Û›· ÂÈÁÔÓ·Ù›‰ˆÓ Î·È Ï·ÁfiÓȘ ÂÍÔÛÙÒÛÂȘ.
™ÙÔ 25% ÙˆÓ ÂÚÈÙÒÛÂˆÓ Û˘Ó˘¿Ú¯ÂÈ ÓÂÊÚÔ¿ıÂÈ· ¿ÏÏÔÙ ¿ÏÏ˘ ‚·Ú‡ÙËÙ·˜ Î·È ÔÛÔÛÙfi 10% ÊÙ¿ÓÂÈ Û ÙÂÏÈÎfi ÛÙ¿‰ÈÔ ÓÂÊÚÈ΋˜ ·Ó¿ÚÎÂÈ·˜ (15). ∏ ÓÂÊÚÈ΋ Û˘ÌÌÂÙÔ¯‹ ‰È·ÎÚ›ÓÂÙ·È Û Ì›˙ÔÓ· Î·È ÂÏ¿ÛÛÔÓ·. ªÂ›˙ˆÓ ¯·Ú·ÎÙËÚ›˙ÂÙ·È Ë ÌÈÎÚÔÛÎÔÈ΋ ·ÈÌ·ÙÔ˘Ú›·, Ë ÚˆÙÂ˚ÓÔ˘Ú›·, ÙÔ Û‡Ó‰ÚÔÌÔ
Alport, Ë ÛÂÈÚ·Ì·ÙÔÓÂÊÚ›Ùȉ·, ÙÔ ÓÂÊÚˆÛÈÎfi Û‡Ó‰ÚÔÌÔ, ÙÔ Ô›‰ËÌ·, Ë ˘¤ÚÙ·ÛËηÈË ÓÂÊÚÈ΋ ·Ó¿ÚÎÂÈ· Î·È ÂÏ¿ÛÛˆÓ Ë ÓÂÊÚÔÏÈı›·ÛË, ÔÈ Û˘ÁÁÂÓ›˜ ‰È·Ì·Úٛ˜ Ô˘ÚËÙ‹ÚˆÓ Î·È ÔÈ ‰È·Ì·Úٛ˜ ·ÛÙˆ˜. ¶ÈÔ Û¿ÓÈ·, Û˘Ó‰˘¿˙ÂÙ·È Ì ÔÊı·ÏÌÈΤ˜ ·ÓˆÌ·Ï›Â˜ (ÌÈÎÚÔʷΛ·, ηٷÚÚ¿ÎÙË, ÎÂÚ·ÙfiΈÓÔ, ÁÏ·‡ÎˆÌ·), ÔÏ˘·ÚÙËÚ›Ùȉ·, ÓÔÛ‹Ì·Ù· ÙÔ˘ Û˘Ó‰ÂÙÈÎÔ‡ ÈÛÙÔ‡ (Û. Goodpasture) Î·È Û¯ÈÛٛ˜ (68,16). ¶ÚfiÛÊ·Ù·, ‰ËÌÔÛȇÙËΠÂÚ›ÙˆÛË Á˘Ó·›Î·˜ Ì NPS Î·È ªELAS, ‰Â›¯ÓÔÓÙ·˜ Èı·Ó‹ Û˘Û¯¤ÙÈÛË ÙÔ˘ Û˘Ó‰ÚfiÌÔ˘ Ì ·ÓˆÌ·Ï›Â˜ Ù˘ ·Ó·Ó¢ÛÙÈ΋˜ ·Ï‡ÛÔ˘ (17).
∏
ÓÂÊÚÈ΋ Û˘ÌÌÂÙÔ¯‹ Ê·›ÓÂÙ·È Ó· ηıÔÚ›˙ÂÙ·È
ÁÂÓÂÙÈο ·fi Ì›· Ó¤· ÌÂÙ¿ÏÏ·ÍË, Ë ÔÔ›· ÚfiÛÊ·Ù· Èı·ÓÔÏÔÁÂ›Ù·È ˆ˜ ˘Â‡ı˘ÓË (12). ∆Ô ÁÔÓ›‰ÈÔ LMX1B Ú˘ıÌ›˙ÂÈ ¿ÌÂÛ· ÙËÓ ·ÚÔ˘Û›· ÙˆÓ ‚·ÛÈÎÒÓ
ÚˆÙÂ˚ÓÒÓ (·3 Î·È ·4) ÙÔ˘ ÎÔÏÏ·ÁfiÓÔ˘ πV, Ô˘
·ÔÙÂÏ› ÙÔ Î‡ÚÈÔ ‰ÔÌÈÎfi Û˘ÛÙ·ÙÈÎfi Ù˘ ‚·ÛÈ΋˜
ÌÂÌ‚Ú¿Ó˘ ÙÔ˘ ÛÂÈÚ¿Ì·ÙÔ˜ (µª™). ∏ ÌÂÙ¿ÏÏ·ÍË
·˘ÙÔ‡ Ê·›ÓÂÙ·È fiÙÈ ·ÔÚÚ˘ıÌ›˙ÂÈ ÙËÓ ÈÛÔÚÚÔ›· ÙˆÓ ·3 Î·È ·4 ÚˆÙÂ˚ÓÒÓ Ù˘ µª™, Ì ·ÔÙ¤ÏÂÛÌ·
ÙË ÓÂÊÚÔ·ıÔÏÔÁÈ΋ ÂÈÎfiÓ· ÙÔ˘ NPS. ∞ÛıÂÓ›˜ ÌÂ
NPS Î·È ÓÂÊÚˆÛÈÎfi Û‡Ó‰ÚÔÌÔ ‹ ¿ÏÏË Û˘Ó‰˘·Ṳ̂-
ÓË ÓÂÊÚÈ΋ ÓfiÛÔ ¯·Ú·ÎÙËÚ›˙ÔÓÙ·È ·fi Ù˘ÈΤ˜ ‰Ô-
ÌÈΤ˜ ·ÓˆÌ·Ï›Â˜ ÛÙË µª™, Ì ÌÂȈ̤ÓË ·ÚÔ˘Û›· ·3 Î·È ·4 ÚˆÙÂ˚ÓÒÓ (18,19).
∏ ‰È¿ÁÓˆÛË ÂȂ‚·ÈÒÓÂÙ·È ·ÂÈÎÔÓÈÛÙÈο ηÈ
ÁÂÓÂÙÈο. ∏ ·ÚÔ˘Û›· ÔÓ˘¯Ô‰˘ÛÏ·Û›·˜ Î·È ÙÂÚ˘Á›ˆÓ Ì ۇÁη„Ë ÛÙÔ˘˜ ·ÁÎÒÓ˜, ηıÒ˜ Î·È Ô ·ÎÙÈÓÔÏÔÁÈÎfi˜ ¤ÏÂÁ¯Ô˜ ÛÙËÓ ·ÛıÂÓ‹ Ì·˜, ÛÙÔÓ ÔÔ›Ô ‰È·ÈÛÙÒıËΠ·Ô˘Û›· ÂÈÁÔÓ·Ù›‰ˆÓ Î·È Ï·ÁfiÓȘ
ÂÍÔÛÙÒÛÂȘ, ¤ıÂÛ·Ó ÙË ‰È¿ÁÓˆÛË ÙÔ˘ Û˘Ó‰ÚfiÌÔ˘. ∏ ·ÚÔ˘Û›· ÙˆÓ Ï·ÁÔÓ›ˆÓ ÂÍÔÛÙÒÛÂˆÓ Â›Ó·È ·ıÔÁÓˆÌÔÓÈÎfi ‡ÚËÌ· ÙÔ˘ Û˘Ó‰ÚfiÌÔ˘. À¿Ú¯ÂÈ ÛÙÔ
80% ÙˆÓ ÂÚÈÙÒÛÂˆÓ Î·È ··ÓÙ¿Ù·È ÌfiÓÔ ÛÙÔ ¡PS (20). (¢˘ÛÙ˘¯Ò˜, ÔÈ ·ÎÙÈÓÔÁڷʛ˜ ·fi ÙȘ Ï·ÁfiÓȘ ÂÍÔÛÙÒÛÂȘ ·ÚÂÏ‹ÊıËÛ·Ó ·fi ÙÔ˘˜ ÁÔÓ›˜
ÚÈÓ ˘¿ÚÍÂÈ ‰˘Ó·ÙfiÙËÙ· ʈÙÔÁÚ¿ÊÈÛ‹˜ ÙÔ˘˜. ∂ÈϤÔÓ, ÔÈ ÁÔÓ›˜ ‰ÂÓ ÚÔ¯ÒÚËÛ·Ó Û ÁÂÓÂÙÈÎfi ¤ÏÂÁ¯Ô).
O ¤ÏÂÁ¯Ô˜ Ù˘ ÏÂÈÙÔ˘ÚÁ›·˜ ‚·ÛÈÎÒÓ ÔÚÁ¿ÓˆÓ, fiˆ˜ ÓÂÊÚÒÓ Î·È ÔÊı·ÏÌÒÓ, ηıÒ˜ ›Û˘ Ô ¤ÏÂÁ¯Ô˜ ÙÔ˘ ÌÂÙ·‚ÔÏÈÛÌÔ‡ ÙÔ˘ ·Û‚ÂÛÙ›Ô˘ Î·È ÓÔÛËÌ¿ÙˆÓ Û˘Ó‰ÂÙÈÎÔ‡ ÈÛÙÔ‡, Â›Ó·È ··Ú·›ÙËÙ·. ™ÙËÓ ·ÛıÂÓ‹ Ì·˜ ‰ÂÓ ‰È·ÈÛÙÒıËÎ·Ó Û˘Ó˘¿Ú¯Ô˘Û˜ ‰È·Ù·Ú·¯¤˜.
¢È·ÊÔÚÈ΋ ‰È¿ÁÓˆÛË ÙÔ˘ Û˘Ó‰ÚfiÌÔ˘ ı· Ú¤ÂÈ Ó· Á›ÓÂÈ ·fi ¿ÏÏ· ÓÔÛ‹Ì·Ù· ‹ ηٷÛÙ¿ÛÂȘ Ô˘ ·ÚÔ˘ÛÈ¿˙ÔÓÙ·È Ì ۇÁÎ·Ì„Ë ·ÁÎÒÓ·, fiˆ˜ ÙÔ Û‡Ó‰ÚÔÌÔ “Escobar” (Multiple Pterygium Syndrome) fiÔ˘ ·Ó¢ڛÛÎÔÓÙ·È ÙÂÚ‡ÁÈ· Î·È ‰˘ÛϷۛ˜ ÂÈÁÔÓ·Ù›‰ˆÓ Î·È Û˘¯Ó¿ Û˘Ó˘¿Ú¯Ô˘Ó ÌÈÎÚÔÁÓ·ı›·, ·ÙÂϤ˜ Ï˘ÎfiÛÙÔÌ·, ÙÂÚ‡ÁÈÔ ÙÚ·¯‹ÏÔ˘, ηÌÙÔ‰·ÎÙ˘-
Ï›· ‹ Û˘Ó‰·ÎÙ˘Ï›·, ÎÚ˘„ÔÚ¯›·, ÛÎÔÏ›ˆÛË, ·ʈÛË Î·È Ó·ÓÈÛÌfi˜ Î·È ÙÔ Û‡Ó‰ÚÔÌÔ ÎÓËÌÈ·›ˆÓ ÙÂÚ˘Á›ˆÓ, ÙÔ ÔÔ›Ô Û˘Ó‰˘¿˙ÂÈ ÎÓËÌÈ·›Â˜ Ù˘¯¤˜, Û˘Ó‰·ÎÙ˘Ï›·, Û¯ÈÛٛ˜, ÎÚ˘„ÔÚ¯›·, ‰˘ÛÏ·Û›· ÔÛ¯¤Ô˘(13).
∞ÛıÂÓ›˜ Ì NPS Ô˘ ·ÚÔ˘ÛÈ¿˙Ô˘Ó Û˘ÁÁÂÓ‹ Û‡ÁÎ·Ì„Ë ·ÁÎÒÓˆÓ, ¯ˆÚ›˜ ÓÂÊÚÈ΋ ‹ ¿ÏÏË Û˘ÛÙËÌ·ÙÈ΋ ÓfiÛÔ (ÎÔÏÏ·ÁfiÓˆÛË, ·ÁÁÂÈ›Ùȉ·, ÔÊı·ÏÌÈ΋
¿ıËÛË), ‰‡Ó·ÓÙ·È Ó· ·ÔÎÙ‹ÛÔ˘Ó ÌÂÙ¿ ·fi ¯ÂÈÚÔ˘ÚÁÈ΋ ·ÔηٿÛÙ·ÛË, ‚ÂÏÙ›ˆÛË Ù˘ ÁˆÓ›·˜
ο̄˘ ÙÔ˘ ·ÁÎÒÓ· Î·È Ó· ‰È¿ÁÔ˘Ó Û¯Â‰fiÓ Ê˘ÛÈÔÏÔÁÈÎfi ‚›Ô, ·ÚÎÒ˜ ·˘ÙÔÂ͢ËÚÂÙÔ‡ÌÂÓÔÈ. ∏ ¯Ú‹ÛË Û˘Ó‰˘·Ṳ̂Ó˘ ıÂڷ›·˜ ‰˘Ó·ÌÈÎÒÓ Ó·Úı‹ÎˆÓ
ÚÔÂÁ¯ÂÈÚËÙÈο ηÈ, ·ÎÔÏÔ‡ıˆ˜, Ë ¯ÂÈÚÔ˘ÚÁÈ΋ ·ÔηٿÛÙ·ÛË Ù˘ Û‡Áη̄˘ ÙˆÓ ·ÁÎÒÓˆÓ
(fiˆ˜ ¤ÁÈÓ Ì ÙËÓ ·ÛıÂÓ‹ Ô˘ ÂÚÈÁÚ¿ÊÂÙ·È) ÂÈÙ˘Á¯¿ÓÂÈ ÌÂÁ·Ï‡ÙÂÚË ¤ÎÙ˘ÍË (ÂÚ›Ô˘ 155-160
ÌÔ›Ú˜). ∏ ÌÂÙÂÁ¯ÂÈÚËÙÈ΋ ÂÊ·ÚÌÔÁ‹ ‰˘Ó·ÌÈÎÔ‡
Ó¿ÚıËη ÁÈ· ‰È¿ÛÙËÌ· ÌÂÁ·Ï‡ÙÂÚÔ ‹ ›ÛÔ ÙÔ˘ ÂÍ·Ì‹ÓÔ˘, Ì ÙÔÓ ÔÔ›Ô ı· Á›ÓÂÙ·È Û˘Ó¯‹˜ ¿ÛÎËÛË
‰È·Ù·ÙÈÎÒÓ ‰˘Ó¿ÌÂˆÓ ÛÙ· ı˘Ï·ÎÔÛ˘Ó‰ÂÛÌÈο ÛÙÔȯ›· (‰˘Ó¿ÌÂȘ ÂÚ˘ÛÌÔ‡), ÛÙ·ıÂÚÔÔÈ› ÙÔ ¯ÂÈÚÔ˘ÚÁÈÎfi ·ÔÙ¤ÏÂÛÌ· ¤ÛÙˆ Î·È ·Ó Ë ÂÊ·ÚÌÔÁ‹ Á›ÓÂÙ·È ÌÂÚÈÎÒ˜ ‹ ηٿ ÙË ‰È¿ÚÎÂÈ· Ù˘ Ó‡ÎÙ·˜. ∆Ô ·ÙÂϤ˜, fï˜, ·ÈÛıËÙÈÎfi Î·È ÏÂÈÙÔ˘ÚÁÈÎfi ·ÔÙ¤ÏÂÛÌ· ÚÔ‚ÏËÌ·Ù›˙ÂÈ ÔÏÏÔ‡˜ ·ÛıÂÓ›˜, ¯ˆÚ›˜ fï˜ ̤¯ÚÈ Û‹ÌÂÚ· Ó· ˘¿Ú¯ÂÈ ‰˘Ó·ÙfiÙËÙ· Ï‹ÚÔ˘˜
·ÔηٿÛÙ·Û˘.
∞ÛıÂÓ›˜ Ì NPS ÙÂÎÓÔÔÈÔ‡Ó ·È‰È¿ Ì ÙÔ Û‡Ó‰ÚÔÌÔ (·˘ÙÔۈ̷ÙÈÎfi ÂÈÎÚ·ÙÔ‡Ó ÁÔÓ›‰ÈÔ). O ΛӉ˘ÓÔ˜ ·Ó¿Ù˘Í˘ ÓÂÊÚÈ΋˜ ÓfiÛÔ˘ Â›Ó·È 25% Î·È ÓÂÊÚÈ΋˜ ·Ó¿ÚÎÂÈ·˜ 10% (15).
∏ ‰È¿ÁÓˆÛË ÙÔ˘ Û˘Ó‰ÚfiÌÔ˘ Ì ÚÔÁÂÓÓËÙÈÎfi
¤ÏÂÁ¯Ô Â›Ó·È Û‹ÌÂÚ· ÂÊÈÎÙ‹ Ì ˘ÂÚ‹¯Ô˘˜Î·È ÌÂ
ÌÔÚȷ΋ ·Ó¿Ï˘ÛË DNA (21). °ÂÓÈο, Ë ÙÂÎÓÔÔ›ËÛË Û ÔÈÎÔÁ¤ÓÂȘ Ì NPS ·Ôı·ÚÚ‡ÓÂÙ·È ·ÊÂÓfi˜ ÁÈ· ÙÔÓ Î›Ó‰˘ÓÔ Û˘Ó‡·Ú͢ ÓÂÊÚÈÎÒÓ ‚Ï·‚ÒÓ, ·ÊÂÙ¤ÚÔ˘ ÁÈ· Ó· ÂÚÈÔÚÈÛÙ› Ô ·ÚÈıÌfi˜ ÊÔÚ¤ˆÓ ÓÔÛËÚÒÓ ÁÔÓȉ›ˆÓ ÙÔ˘ Û˘Ó‰ÚfiÌÔ˘(15).∂›Ó·È, fï˜, ÁÂÁÔÓfi˜ fiÙÈ Û‹ÌÂÚ· ÌÔÚ› Ó· Ú·ÁÌ·ÙÔÔÈËı› ÚÔÁÂÓÓËÙÈ΋ ‚ÈÔ„›· ÓÂÊÚÔ‡ (22), ÒÛÙ ¤ÁηÈÚ· Ó· ‰È·ÈÛÙÒÓÂÙ·È Ë Û˘Ó‡·ÚÍË ‹ ÌË ÓÂÊÚÈ΋˜ ÓfiÛÔ˘ ÛÙÔ ¤Ì‚Ú˘Ô, ¯ˆÚ›˜ fï˜ ¿ÓÙ· Ó· Â›Ó·È ‰˘Ó·Ùfi˜ Ô Î·ıÔÚÈÛÌfi˜ Ù˘ Û Ì›˙ÔÓ· ‹ ÂÏ¿ÛÛÔÓ· ÓÂÊÚÈ΋ ‚Ï¿‚Ë.
µÈ‚ÏÈÔÁÚ·Ê›·
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18.Morello R, Zhou G, Dreyer SD, Harvey SJ, Ninomiya Y, Thorner PS et al. Regulation of glomerular basement membrane collagen expression by LMX1B contributes to renal disease in nail patella syndrome. Nat Genet 2001;27:205-208.
19. Rohr C, Prestel J, Heidet L, Hosser H, Kriz W, Johnson RL et al. The LIM-homeodomain transcription factor Lmx1b plays a crucial role in podocytes. J Clin Invest 2002;109:10731082.
20. Goshen E, Schwartz A, Zilka LR, Zwas ST. Bilateral accessory iliac horns: pathognomonic findings in Nailpatella syndrome. Scintigraphic evidence on bone scan. Clin Nucl Med 2000;25:476-477.
21. Pinette MG, Ukleja M, Blackstone J. Early prenatal diagnosis of nail-patella syndrome by ultrasonography. J Ultrasound Med 1999;18:387-389.
22. Gubler MC, Levy M. Prenatal diagnosis of nail-patella syndrome by kidney biopsy. Am J Med Genet 1993;43:693-696.
∏ÌÂÚÔÌËÓ›· ˘Ô‚ÔÏ‹˜: 27-08-2002
∏ÌÂÚÔÌËÓ›· ¤ÁÎÚÈÛ˘: 12-12-2002
¢È‡ı˘ÓÛË ·ÏÏËÏÔÁÚ·Ê›·˜: ¶··‰ÔÔ‡ÏÔ˘ ∞ıËÓ¿
¶·È‰È·ÙÚÈÎfi ∆Ì‹Ì·, °.¶.¡. “∫∞∆”
∆.∫. 145 61, ∫ËÊÈÛÈ¿
§··ÚÔÛÎÔÈ΋ ·ÓÙÈÌÂÙÒÈÛË Û˘ÁÁÂÓÔ‡˜ ÌÂÁ¿ÎÔÏÔ˘ Û ÓÂÔÁÓfi.
¶ÂÚÈÁÚ·Ê‹ ÂÚ›ÙˆÛ˘
∂. ¶··Ó‰Ú¤Ô˘, ∂. µ·ÛÈÏÂÈ¿‰Ô˘, ∂. §ÂÈ‚·‰›ÙË, ∂. °ÎÔ˘ÁÎÔ‡‰Ë, ™. ™˘Ú¿ÎÔ˜, ™. ∞ÚÁ˘ÚÔ‡, ™. ¡ÈÎÔÏ¿Ô˘, ¢. ∫ÂÚ·Ì›‰·˜
Laparoscopic treatment of congenital megacolon in a newborn infant.
A case report
E. Papandreou, E. Vasiliadou, E. Livaditi, E. Gougoudi, S. Spyrakos, S. Argyrou, S. Nikolaou, D. Keramidas ∂¡¢π∞º∂ƒOÀ™∞
¶ÂÚ›ÏË„Ë: ∆Ô Û˘ÁÁÂÓ¤˜ ÌÂÁ¿ÎÔÏÔ ÛÙË ÓÂÔÁÓÈ΋ ËÏÈΛ· Û˘Ó‹ıˆ˜ ÂΉËÏÒÓÂÙ·È Ì ÂÈÎfiÓ· ·fiÊڷ͢ ÙÔ˘ ÂÓÙ¤ÚÔ˘ Ô˘ ÌÔÚ› Ó· ÂÈϯı› ÌÂ
ÂÓÙÂÚÔÎÔÏ›Ùȉ·, Ë ÔÔ›· ·ÓÙÈÌÂÙˆ›˙ÂÙ·È Ì Â›ÁÔ˘Û· ÎÔÏÔÛÙÔÌ›·. ∏ ·ÔηٿÛÙ·ÛË Ù˘ Û˘ÁÁÂÓÔ‡˜ ·ÓˆÌ·Ï›·˜ Á›ÓÂÙ·È Û ‰Â‡ÙÂÚÔ ¯ÂÈÚÔ˘ÚÁÈÎfi
¯ÚfiÓÔ. ¶ÂÚÈÁÚ¿ÊÂÙ·È Ë ÚÒÙË ÂÚ›ÙˆÛË ÛÙËÓ ÂÏÏËÓÈ΋ ‚È‚ÏÈÔÁÚ·Ê›· ÓÂÔÁÓÔ‡ ÌÂ Û˘ÁÁÂÓ¤˜ ÌÂÁ¿ÎÔÏÔ, ÙÔ ÔÔ›Ô ¯ÂÈÚÔ˘ÚÁ‹ıËΠϷ·ÚÔÛÎÔÈο Û ¤Ó· ¯ÂÈÚÔ˘ÚÁÈÎfi ¯ÚfiÓÔ ¯ˆÚ›˜ ÎÔÏÔÛÙÔÌ›·. ∆Ô ÓÂÔÁÓfi ·ÚÔ˘Û›·Û ÛËÌ›· ÂÓÙÂÚÈ΋˜ ·fiÊڷ͢, fiˆ˜ ›ۯÂÛË ·ÂÚ›ˆÓ Î·È ÎÔÚ¿ÓˆÓ Î·È ÌÂÙˆÚÈÛÌfi ÎÔÈÏ›·˜. ¶ÚÔÂÁ¯ÂÈÚËÙÈο ¯ÔÚËÁ‹ıËΠÔÏÈ΋
·ÚÂÓÙÂÚÈ΋ ‰È·ÙÚÔÊ‹, ·ÓÙÈ‚›ˆÛË Î·È ¤ÁÈÓ ÚÔÂÙÔÈÌ·Û›· ÙÔ˘ ·¯¤Ô˜ ÂÓÙ¤ÚÔ˘. ™ÙÔ ¯ÂÈÚÔ˘ÚÁ›Ô
¤ÁÈÓ Ϸ·ÚÔÛÎÔÈ΋ ··ÁÁ›ˆÛË ÙÔ˘ ·ıÔÏÔÁÈÎÔ‡ ÂÓÙ¤ÚÔ˘, ·Ó¿‰ÚÔÌË ‰È·ÚˆÎÙÈ΋ ‚ÏÂÓÓÔÁÔÓÂÎÙÔÌ‹ ÙÔ˘ ÔÚıÔ‡, ‰ÈÂ΂ÔÏ‹ Î·È Â͈ÙÂڛ΢ÛË ÙÔ˘ ·¯¤Ô˜ ÂÓÙ¤ÚÔ˘ ̤ۈ ÙÔ˘ ·Ô‚ÏÂÓÓÔÁÔÓÈṲ̂ÓÔ˘
Ì˘˚ÎÔ‡ ÎÔÏÔ‚ÒÌ·ÙÔ˜ ÙÔ˘ ÔÚıÔ‡ Î·È ÙÂÏÈÎÔ-ÙÂÏÈ΋ ÂÓÙÂÚÔÚˆÎÙÈ΋ ·Ó·ÛÙfïÛË. ∏ ÌÂÙÂÁ¯ÂÈÚËÙÈ΋ ÔÚ›· ÙÔ˘ ÓÂÔÁÓÔ‡ ‹Ù·Ó ÔÌ·Ï‹ Î·È Ë ÏÂÈÙÔ˘ÚÁ›·
ÙÔ˘ ÂÓÙ¤ÚÔ˘ ·ÔηٷÛÙ¿ıËΠϋڈ˜.
§¤ÍÂȘ ÎÏÂȉȿ: Û˘ÁÁÂÓ¤˜ ÌÂÁ¿ÎÔÏÔ, ÓÂÔÁÓfi, Ï··ÚÔÛÎÔÈ΋ ¯ÂÈÚÔ˘ÚÁÈ΋.
∂ÈÛ·ÁˆÁ‹ ∆Ô Û˘ÁÁÂÓ¤˜ ÌÂÁ¿ÎÔÏÔ ÛÙË ÓÂÔÁÓÈ΋ ËÏÈΛ· ÂΉËÏÒÓÂÙ·È Ì ÂÈÎfiÓ· ÂÓÙÂÚÈ΋˜ ·fiÊڷ͢. ∞ÓÙÈÌÂÙˆ›˙ÂÙ·È Ì ÂÚ¢ÓËÙÈ΋ Ï··ÚÔÙÔÌ›·, Â¿Ó ‰ÂÓ ˘¿Ú¯ÂÈ ÚÔÂÁ¯ÂÈÚËÙÈ΋ ‰È¿ÁÓˆÛË. ∂Áηı›ÛÙ·Ù·È ÎÔÏÔÛÙÔÌ›· ÎÂÓÙÚÈο Ù˘ ·Á·ÁÁÏȷ΋˜ ‹ ˘ÔÁ·ÁÁÏȷ΋˜ ˙ÒÓ˘ Î·È ·ÎÔÏÔ˘ı› Ë ÎÔÈÏÈÔÂÚÈÓÂ˚΋ ÂÁ¯Â›ÚËÛË ·ÔηٿÛÙ·Û˘ ÙÔ˘ ÌÂÁ¿ÎÔÏÔ˘ Û ‰Â‡ÙÂ-
µ’ ¶·È‰Ô¯ÂÈÚÔ˘ÚÁÈÎfi TÌ‹Ì·, ¡ÔÛÔÎÔÌÂ›Ô ¶·›‰ˆÓ “∞Á›· ™ÔÊ›·”, ∞ı‹Ó·
Abstract: Congenital megacolon in newborn infants presents clinically as bowel obstruction. In cases complicated by enterocolitis, emergency colostomy is established, followed later by the definitive, second stage, operation. This is the first report in the Greek literature of congenital megacolon in a neonate submitted to laparoscopic operation without preceding colostomy. The neonate presented with intestinal obstruction. Total parenteral nutrition and intravenous antibiotics were given preoperatively and serial bowel washouts were performed. The aganglionic colon was removed laparoscopically and dissection of the rectal mucosa was performed transanally. The ganglionic colon was pulled through the muscular cuff of the rectum and anastomosed above the dentate line, within the muscular cuff. The postoperative course was uncomplicated and bowel function after the operation was normal.
Key words: congenital megacolon, neonate, laparoscopic surgery.
ÚÔ ÂÁ¯ÂÈÚËÙÈÎfi ¯ÚfiÓÔ (1). OÈ Georgeson Î·È Û˘Ó, ÙÔ 1995, ÂÚȤÁÚ·„·Ó ÙËÓ Ù¯ÓÈ΋ Ï··ÚÔÛÎÔÈ΋˜ ÂÁ¯Â›ÚËÛ˘ ÙÔ˘ Û˘ÁÁÂÓÔ‡˜ ÌÂÁ¿ÎÔÏÔ˘ (2). ª¤¯ÚÈ Û‹ÌÂÚ·, ÂÏ¿¯ÈÛÙ˜ Â›Ó·È ÔÈ ·Ó·ÊÔÚ¤˜ ÛÙË Ï··ÚÔÛÎÔÈ΋ ·ÓÙÈÌÂÙÒÈÛË ÙÔ˘ Û˘ÁÁÂÓÔ‡˜ ÌÂÁ¿ÎÔÏÔ˘ ÛÙË ÓÂÔÁÓÈ΋ ËÏÈΛ·. ¶ÂÚÈÁÚ¿ÊÂÙ·È Ë ÚÒÙË ÂÚ›ÙˆÛË ÛÙËÓ ÂÏÏËÓÈ΋ ‚È‚ÏÈÔÁÚ·Ê›·, Ï··ÚÔÛÎÔÈ΋˜ ·ÓÙÈÌÂÙÒÈÛ˘ ÓÂÔÁÓÔ‡ ÌÂ Û˘ÁÁÂÓ¤˜ ÌÂÁ¿ÎÔÏÔ.
2nd Paediatric Surgical Department, “Ag. Sophia”Children’s Hospital, Athens
¶ÂÚÈÁÚ·Ê‹ ÂÚ›ÙˆÛ˘
¡ÂÔÁÓfi ¿ÚÚÂÓ ËÏÈΛ·˜ 15 ËÌÂÚÒÓ, Ì µ° 3210 g, ÓÔÛËχıËΠÁÈ·Â̤ÙÔ˘˜ Î·È ‰È¿Ù·ÛË ÎÔÈÏ›·˜ ÏfiÁˆ
›ۯÂÛ˘ ·ÂÚ›ˆÓ Î·È ÎÔÚ¿ÓˆÓ. ∞fi ÙÔÓ ÎÏÈÓÈÎfi
Î·È ÂÚÁ·ÛÙËÚÈ·Îfi ¤ÏÂÁ¯Ô ÂÙ¤ıË Ë ‰È¿ÁÓˆÛË ÙÔ˘
Û˘ÁÁÂÓÔ‡˜ ÌÂÁ¿ÎÔÏÔ˘ (∂ÈÎfiÓ· 1).
∏ ÚÔÂÁ¯ÂÈÚËÙÈ΋ ÂÙÔÈÌ·Û›· ÂÚÈÂÏ¿Ì‚·Ó ‰È·ÎÔ-
‹ Ù˘ Û›ÙÈÛ˘, ¯ÔÚ‹ÁËÛË ÔÏÈ΋˜ ·ÚÂÓÙÂÚÈ΋˜ ‰È·-
ÙÚÔÊ‹˜ Î·È ÂÓ‰ÔÊϤ‚È·˜ ·ÓÙÈ‚›ˆÛ˘, ηıÒ˜ Î·È ÚÔ-
ÂÙÔÈÌ·Û›· ÙÔ˘ ÂÓÙ¤ÚÔ˘, ÙÔ ÂÚȯfiÌÂÓÔ ÙÔ˘ ÔÔ›Ô˘
ÂÎÎÂÓÒıËΠÌÂ Û˘¯Ó¤˜, ·ӷϷ̂·ÓfiÌÂÓ˜ ÙÔÔıÂ-
Ù‹ÛÂȘ ۈϋӷ ·ÂÚ›ˆÓ Î·È Ï‡ÛÂȘ ÌÂ Ê˘ÛÈÔÏÔÁÈÎfi
ÔÚfi. ∏ ÂÁ¯Â›ÚËÛË ¤ÁÈÓ Ϸ·ÚÔÛÎÔÈο, ¯ˆÚ›˜ ÎÔÏÔ-
ÛÙÔÌ›·. ∏ ¤ÎÙ·ÛË Ù˘ ·Á·ÁÁÏȷ΋˜ Î·È ˘ÔÁ·ÁÁÏÈ·-
΋˜ ˙ÒÓ˘ ηıÔÚ›ÛÙËΠ̠ٷ¯Â›Â˜ ‚ÈÔ„›Â˜ ηٿ ÙË
Ï··ÚÔÛÎÔÈ΋ Ê¿ÛË Ù˘ ÂÁ¯Â›ÚËÛ˘ Î·È ·ÊÔÚÔ‡ÛÂ
ÛÙÔ ÔÚıfi Î·È ÙÔ Î¿Ùˆ ÙÚÈÙËÌfiÚÈÔ ÙÔ˘ ÛÈÁÌÔÂȉԇ˜. ∏
··ÁÁ›ˆÛË ÙÔ˘ ·ıÔÏÔÁÈÎÔ‡ ÙÌ‹Ì·ÙÔ˜ ÙÔ˘ ·¯¤Ô˜
ÂÓÙ¤ÚÔ˘ Î·È Ë ÎÈÓËÙÔÔ›ËÛË ·˘ÙÔ‡ ¤ÁÈÓ Ϸ·ÚÔÛÎÔ-
Èο. ÃÚËÛÈÌÔÔÈ‹ıËÎ·Ó 3 trocar, 1 ÁÈ· ÙËÓ Î¿ÌÂÚ·
Î·È 2 ÁÈ· Ù· ÂÚÁ·Ï›· ÂÚÁ·Û›·˜. ∏ ›ÂÛË ÙÔ˘ CO2 ΢-
Ì¿ÓıËΠ۠›‰· 3-5 mmHg. ∞ÎÔÏÔ‡ıËÛÂ Ô ÂÚÈ-
ÓÂ˚Îfi˜ ¯ÚfiÓÔ˜, Ô ÔÔ›Ô˜ ÂÚÈÂÏ¿Ì‚·Ó ·Ó¿‰ÚÔÌË
‰È·ÚˆÎÙÈ΋ ‚ÏÂÓÓÔÁÔÓÂÎÙÔÌ‹ ÙÔ˘ ÔÚıÔ‡ (∂ÈÎfiÓ· 2), ‰ÈÂ΂ÔÏ‹ Î·È Â͈ÙÂڛ΢ÛË ÙÔ˘ ·¯¤Ô˜ ÂÓÙ¤ÚÔ˘ ̤ۈ ÙÔ˘ ·Ô‚ÏÂÓÓÔÁÔÓÈṲ̂ÓÔ˘ ÎÔÏÔ‚ÒÌ·ÙÔ˜ ÙÔ˘ ÔÚ-
ıÔ‡ (∂ÈÎfiÓ· 3) Î·È ÙÂÏÈÎÔ-ÙÂÏÈ΋ ÎÔÏÔÚˆÎÙÈ΋ ·Ó·-
ÛÙfïÛË. ∏ ÌÂÙÂÁ¯ÂÈÚËÙÈ΋ ÔÚ›· ÙÔ˘ ÓÂÔÁÓÔ‡ ‹Ù·Ó
ÔÌ·Ï‹ Î·È Ë ÏÂÈÙÔ˘ÚÁ›· ÙÔ˘ ÂÓÙ¤ÚÔ˘ ÌÂÙ¿ ÙËÓ ÂÁ¯Â›ÚËÛË Ê˘ÛÈÔÏÔÁÈ΋.
™˘˙‹ÙËÛË
∆Ô Û˘ÁÁÂÓ¤˜ ÌÂÁ¿ÎÔÏÔ ÛÙË ÓÂÔÁÓÈ΋ ËÏÈΛ·, Û˘Ó‹ıˆ˜ ÂΉËÏÒÓÂÙ·È Ì ÂÈÎfiÓ· ·fiÊڷ͢ ÙÔ˘
·¯¤Ô˜ ÂÓÙ¤ÚÔ˘, Ô˘ ¯·Ú·ÎÙËÚ›˙ÂÙ·È ·fi Â̤ÙÔ˘˜,
∂ÈÎfiÓ· 1. ¢È¿‚·ÛË ÙÔ˘ ·¯¤Ô˜ ÂÓÙ¤ÚÔ˘ Ì ‚¿ÚÈÔ. ∂ÈÎfiÓ·
Û˘ÁÁÂÓÔ‡˜ ÌÂÁ¿ÎÔÏÔ˘.
ÌÂÙˆÚÈÛÌfi ÎÔÈÏ›·˜ Î·È Â›Û¯ÂÛË ·ÂÚ›ˆÓ Î·È ÎÔÚ¿ÓˆÓ. ∏ ÙÔÔı¤ÙËÛË ÛˆÏ‹Ó· ·ÂÚ›ˆÓ ÛÙÔ ÔÚıfi ÂÍÔ˘‰ÂÙÂÚÒÓÂÈ ÙË Û‡Û·ÛË ÙÔ˘ ·Á·ÁÁÏÈ·ÎÔ‡ ̤ÚÔ˘˜ Î·È ·ÎÔÏÔ˘ıÂ›Ù·È ·fi ÂÎÚËÎÙÈ΋ ·Ô‚ÔÏ‹ ·ÂÚ›ˆÓ Î·È ÎÔÚ¿ÓˆÓ, ÂÊfiÛÔÓ Ô ÛˆÏ‹Ó·˜ ¤¯ÂÈ Ì‹ÎÔ˜ fiÛÔ Î·È ÙÔ - Û ۇ۷ÛË - ¤ÓÙÂÚÔ (3). ™˘¯Ó‹ ÂÈÏÔ΋ ÙÔ˘ Û˘ÁÁÂÓÔ‡˜ ÌÂÁ¿ÎÔÏÔ˘ ÛÙË ÓÂÔÁÓÈ΋ ËÏÈΛ· Â›Ó·È Ë ÂÓÙÂÚÔÎÔÏ›ÙȘ, Ë ÔÔ›· ··ÈÙ› ›ÁÔ˘Û· ÎÔÏÔÛÙÔÌ›·. ∏ ¤ÁηÈÚË ‰È¿ÁÓˆÛË ÙÔ˘ Û˘ÁÁÂÓÔ‡˜ ÌÂÁ¿ÎÔÏÔ˘, Ë ÔÔ›· Á›ÓÂÙ·È Ì ÙËÓ ÎÏÈÓÈ΋ ÂÎÙ›ÌËÛË, ÙË ‚ÈÔ„›· ÙÔ˘ ÔÚıÔ‡ Î·È ÙÔÓ ·ÂÈÎÔÓÈÛÙÈÎfi ¤ÏÂÁ¯Ô, Û˘Ì‚¿ÏÏÂÈ ÛÙËÓ ÚfiÏË„Ë Ù˘ ÂÓÙÂÚÔÎÔÏ›Ùȉ·˜ Î·È ÛÙËÓ ·ÏÏ·Á‹ ÛÙÚ·ÙËÁÈ΋˜ ˆ˜ ÚÔ˜ ÙË
¯ÂÈÚÔ˘ÚÁÈ΋ ·ÓÙÈÌÂÙÒÈÛË. ™ÙË Û˘ÁÎÂÎÚÈ̤ÓË ÂÚ›ÙˆÛË, ¤ÁÈÓ ‰È·ÎÔ‹ Ù˘ Û›ÙÈÛ˘, ÙÔÔı¤ÙËÛË ÚÈÓÔÁ·ÛÙÚÈÎÔ‡ ۈϋӷ, ¯ÔÚ‹ÁËÛË ÔÏÈ΋˜ ·ÚÂÓÙÂÚÈ΋˜ ‰È·ÙÚÔÊ‹˜ Î·È ÂÓ‰ÔÊϤ‚È·˜ ·ÓÙÈ‚›ˆÛ˘, ηıÒ˜ ηÈ
∂ÈÎfiÓ· 2. ∞Ó¿‰ÚÔÌË ‰È·ÚˆÎÙÈ΋ ‚ÏÂÓÓÔÁÔÓÂÎÙÔÌ‹ ÙÔ˘ ÔÚıÔ‡.
∂ÈÎfiÓ· 3. ¢ÈÂ΂ÔÏ‹ Î·È Â͈ÙÂڛ΢ÛË ÙÔ˘ ·Á·ÁÁÏÈ·ÎÔ‡ ÙÌ‹Ì·ÙÔ˜ ÙÔ˘ ·¯¤Ô˜ ÂÓÙ¤ÚÔ˘ ̤ۈ ÙÔ˘ ·Ô‚ÏÂÓÓÔÁÔÓÈṲ̂ÓÔ˘ Ì˘˚ÎÔ‡ ¯ÈÙÒÓ· ÙÔ˘ ÔÚıÔ‡.
Û˘¯Ó‹ ÙÔÔı¤ÙËÛË ÛˆÏ‹Ó· ·ÂÚ›ˆÓ ÛÙÔ ÔÚıfi ÁÈ· ·ÔÛ˘ÌÊfiÚËÛË ÙÔ˘ ·¯¤Ô˜ ÂÓÙ¤ÚÔ˘.
ª¤¯ÚÈ Û‹ÌÂÚ·, ÁÈ· ÙËÓ ·ÔηٿÛÙ·ÛË ÙÔ˘ Û˘Á-
ÁÂÓÔ‡˜ ÌÂÁ¿ÎÔÏÔ˘, ¤¯Ô˘Ó ÂÊ·ÚÌÔÛÙ› ÂÈÙ˘¯Ò˜ ÌÂ
Ï··ÚÔÙÔÌ›· ‰È¿ÊÔÚ˜ Ù¯ÓÈΤ˜, ·fi ÙȘ Ôԛ˜ ÔÈ
ÂÈÎÚ·Ù¤ÛÙÂÚ˜ Â›Ó·È ÔÈ Ù¯ÓÈΤ˜ Swenson, Duhamel Î·È Soave-Boley (4-7). ¶ÚfiÛÊ·Ù·, ÔÈ
Georgeson Î·È Û˘Ó ‰ËÌÔÛ›Â˘Û·Ó ÙË Ï··ÚÔÛÎÔÈ-
΋ ·ÓÙÈÌÂÙÒÈÛË ÙÔ˘ Û˘ÁÁÂÓÔ‡˜ ÌÂÁ¿ÎÔÏÔ˘ Î·È Û ¿ÙÔÌ· ÓÂÔÁÓÈ΋˜ ËÏÈΛ·˜ (2,8). ™ÙËÓ ·ÚÔ‡Û· ÂÚ›-
ÙˆÛË, ηٿ ÙË Ï··ÚÔÛÎÔÈ΋ ··ÁÁ›ˆÛË ÙÔ˘
·ıÔÏÔÁÈÎÔ‡ ÂÓÙ¤ÚÔ˘, Ë ›ÂÛË ÙÔ˘ CO2 ‰È·ÙËÚ‹-
ıËΠ۠¯·ÌËÏ¿ ›‰· 3-5 mmHg. ªÂÙ¿ ÙËÓ
ÂÌÂÈÚ›· Ô˘ ·ÔÎÙ‹ıËΠÛÙȘ Ï··ÚÔÛÎÔÈΤ˜ ÂÁ-
¯ÂÈÚ‹ÛÂȘ ÙÔ˘ Û˘ÁÁÂÓÔ‡˜ ÌÂÁ¿ÎÔÏÔ˘ Û ÂÈÚ·Ì·Ùfi˙ˆ·, ¯ÂÈÚÔ˘ÚÁ‹ıËΠϷ·ÚÔÛÎÔÈο ·È‰› ËÏÈΛ·˜ 14 ÂÙÒÓ ÌÂ Û˘ÁÁÂÓ¤˜ ÌÂÁ¿ÎÔÏÔ, Ì ¿ÚÈÛÙÔ ÌÂÙÂÁ¯ÂÈÚËÙÈÎfi ·ÔÙ¤ÏÂÛÌ· (9,10). ™ÙËÓ ÂÚ›ÙˆÛË ·˘Ù‹, Ë ›ÂÛË ÙÔ˘ CO2 ÛÙËÓ ÂÚÈÙÔÓ·˚΋ ÎÔÈÏfiÙËÙ· ‹Ù·Ó 10±2 mmHg. ∏ ÂÌÂÈÚ›· ·˘Ù‹ ·ÍÈÔÔÈ‹ıËΠηÈ, ¤ÙÛÈ, ¯ÂÈÚÔ˘ÚÁ‹ıËΠϷ·ÚÔÛÎÔÈο ÓÂÔÁÓfi
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7. Boley S. An endorectal pull-through operation with primary anastomosis for Hirschsprung’s disease in infants and children. J Paediatr Surg 1995;30:1017-1022.
8. Georgeson KE, Cohen RD, Hebra A, Jona JZ, Powell DM, Rothenberg SS et al. Primary laparoscopic-assisted endorectal colon pull-through for Hirschsprung’s disease: a new gold standard. Ann Surg 1999;229:678-683.
9. ¶··Ó‰Ú¤Ô˘ ∂, ÃȈٛÓ˘ Ã, ª·ÏÙÔÁÈ¿ÓÓ˘ ¡, ∫Ô˘ÏfiÔ˘ÏÔ˜ ∫, ÷ڛÛË µ, ¶··Ïfi˘ ∞ Î·È Û˘Ó. §··ÚÔÛÎÔÈ΋ ÂÊ·ÚÌÔÁ‹ ÙˆÓ Ù¯ÓÈÎÒÓ Swenson, Duhamel Î·È Soave ÛÙËÓ ·ÓÙÈÌÂÙÒÈÛË Û˘ÁÁÂÓÔ‡˜ ÌÂÁ¿ÎÔÏÔ˘ Û ÂÈÚ·Ì·ÙÈÎfi ÌÔÓÙ¤ÏÔ. §··ÚÔÂÓ‰ÔÛÎÔÈ΋ ÃÂÈÚÔ˘ÚÁÈ΋ 2001;3:7-13. 10. ¶··Ó‰Ú¤Ô˘ ∂, ™˘Ú¿ÎÔ˜ ™, ÷ÚÌ¿Ó˘ °, ª·ÏÙÔÁÈ¿ÓÓ˘ ¡, ∑·¯·ÚfiÔ˘ÏÔ˜ ¢, ∫ÂÚ·Ì›‰·˜ ¢. §··ÚÔÛÎÔÈ΋ ¯ÂÈÚÔ˘ÚÁÈ΋ ÛÙÔ Û˘ÁÁÂÓ¤˜ ÌÂÁ¿ÎÔÏÔ: ¶ÂÚ›ÙˆÛË ·È‰ÈÔ‡ ËÏÈΛ·˜ 14 ÂÙÒÓ. ∂ÏÏËÓÈ΋ ÃÂÈÚÔ˘ÚÁÈ΋ (˘fi ¤Î‰ÔÛË).
HÌÂÚÔÌËÓ›· ˘Ô‚ÔÏ‹˜: 29-07-2002
HÌÂÚÔÌËÓ›· ¤ÁÎÚÈÛ˘: 14-02-2003
¢È‡ı˘ÓÛË ·ÏÏËÏÔÁÚ·Ê›·˜: ∂. ¶··Ó‰Ú¤Ô˘
∆ÚÈfiψ˜ 1, ∆.∫. 151 27, ªÂÏ›ÛÛÈ·
∂¡¢π∞º∂ƒOÀ™∞
∫˘ÛÙÈ΋ ·‰Âӈ̷Ù҉˘ ‰˘ÛÏ·Û›·
¶ÂÚÈÁÚ·Ê‹ ÙÚÈÒÓ ÂÚÈÙÒÛÂˆÓ Î·È ·Ó·ÛÎfiËÛË Ù˘ ‚È‚ÏÈÔÁÚ·Ê›·˜
µ. ¢ÚfiÛÔ˘ - ∞Á·Î›‰Ô˘, ∫. ™·Ú·Ê›‰Ë˜, °. ∫˘ÚȷΛ‰Ë˜, °. ªËÙÛÈ¿ÎÔ˜, °. ∫ÚÂÌÂÓfiÔ˘ÏÔ˜
Cystic adenomatoid malformation of the lung.
Report of three cases and review of the literature
V. Drossou - Agakidou, K. Sarafidis, G. Kyriakidis, G. Mitsiakos, G. Kremenopoulos
¶ÂÚ›ÏË„Ë: ∏ Û˘ÁÁÂÓ‹˜ ΢ÛÙÈ΋ ·‰Âӈ̷Ù҉˘
‰˘ÛÏ·Û›· ÙÔ˘ Ó‡ÌÔÓ· (™∫∞¢¶) ·ÔÙÂÏ› Û¿-
ÓÈÔ, ·ÏÏ¿ ÛÔ‚·Úfi ·›ÙÈÔ ·Ó·Ó¢ÛÙÈ΋˜ ‰˘Û¯¤ÚÂÈ·˜
ÛÙË ÓÂÔÁÓÈ΋ ËÏÈΛ·. ¶ÂÚÈÁÚ¿ÊÔÓÙ·È ÙÚÂȘ ÂÚÈÙÒ-
ÛÂȘ ÓÂÔÁÓÒÓ Ì ™∫∞¢¶, ·ıÔÏÔÁÔ·Ó·ÙÔÌÈο ÙÂÎÌËÚȈ̤Ó˜. ¶ÚfiÎÂÈÙ·È ÁÈ· ‰‡Ô ÎÔÚ›ÙÛÈ· Î·È ¤Ó·
·ÁfiÚÈ, ‰‡Ô ·fi Ù· ÔÔ›· ÂÌÊ¿ÓÈÛ·Ó ·Ó·Ó¢ÛÙÈ΋ ‰˘Û¯¤ÚÂÈ· ·Ì¤Ûˆ˜ ÌÂÙ¿ ÙË Á¤ÓÓËÛË Î·È ¤Ó· ÛÙÔ Ù¤-
ÏÔ˜ ÙÔ˘ 1Ô˘ Ì‹Ó· Ù˘ ˙ˆ‹˜. ¶ÚÔÁÂÓÓËÙÈ΋ ‰È¿ÁÓˆ-
ÛË ¤ÁÈÓ Û ̛· ÂÚ›ÙˆÛË. ªÂÙ¿ ÙË Á¤ÓÓËÛË, Ë ‰È¿-
ÁÓˆÛË ‚·Û›ÛÙËΠÛÙËÓ ÎÏÈÓÈ΋ ÂÈÎfiÓ· Î·È ÛÙ· ¢ڋ-
Ì·Ù· ÙÔ˘ ·ÂÈÎÔÓÈÛÙÈÎÔ‡ ÂϤÁ¯Ô˘ (·ÎÙÈÓÔÁÚ·Ê›·
ıÒڷη, ·ÍÔÓÈ΋ ÙÔÌÔÁÚ·Ê›·). ¢ÂÓ ˘‹Ú¯·Ó ¿ÏϘ
Û˘ÁÁÂÓ›˜ ‰˘ÛϷۛ˜. ™Â fiÏ· Ù· ÓÂÔÁÓ¿ ¤ÁÈÓ ¯ÂÈ-
ÚÔ˘ÚÁÈ΋ ¤̂·ÛË (ıˆÚ·ÎÔÙÔÌ‹ Î·È ÏÔ‚ÂÎÙÔÌ‹)
Û ۇÓÙÔÌÔ ¯ÚÔÓÈÎfi ‰È¿ÛÙËÌ· ÌÂÙ¿ ÙË ‰È¿ÁÓˆÛË. ∏
‰È¿ÁÓˆÛË ÂȂ‚·ÈÒıËΠ·fi ÙËÓ ·ıÔÏÔÁÔ·Ó·ÙÔ-
ÌÈ΋ ÂͤٷÛË, fiÔ˘ ‰È·ÈÛÙÒıËΠfiÙÈ ‰‡Ô ·fi ÙȘ
ÂÚÈÙÒÛÂȘ Ì·˜ ·Ó‹Î·Ó ÛÙÔÓ Ù‡Ô 1 Î·È Ì›· ÛÙÔÓ
Ù‡Ô 4 Ù˘ ÓfiÛÔ˘. ∏ ÂͤÏÈÍË ‹Ù·Ó ηϋ Û ‰‡Ô ·fi
·˘Ù¿ Ù· ÓÂÔÁÓ¿, ÂÓÒ ¤Ó· η٤ÏËÍ ÌÂÙÂÁ¯ÂÈÚËÙÈο ·fi ÛË„·ÈÌ›·.
§¤ÍÂȘ ÎÏÂȉȿ: ·‰Âӈ̷Ù҉˘ ‰˘ÛÏ·Û›· Ó‡ÌÔÓ·, Û˘ÁÁÂÓ›˜ ·ÛÙÂȘ.
∂ÈÛ·ÁˆÁ‹
∏ Û˘ÁÁÂÓ‹˜ ΢ÛÙÈ΋ ·‰Âӈ̷Ù҉˘ ‰˘ÛÏ·Û›·
ÙÔ˘ Ó‡ÌÔÓ· (™∫∞¢¶) ·ÔÙÂÏ› Û¿ÓÈ· ‰˘ÛÏ·Û›· ÙˆÓ Ó¢ÌfiÓˆÓ, ÌÂ Û˘¯ÓfiÙËÙ· Ô˘ ˘ÔÏÔÁ›˙ÂÙ·È Û 1 ÂÚ›ÙˆÛË ·Ó¿ 25000-35000 ΢‹ÛÂȘ (1).
÷ڷÎÙËÚ›˙ÂÙ·È ·fi ÙË ‰ËÌÈÔ˘ÚÁ›· ·ÛÙÂˆÓ ÔÈΛÏÔ˘ ÌÂÁ¤ıÔ˘˜, ÔÈ Ôԛ˜ ÂÓÙÔ›˙ÔÓÙ·È, ηٿ ÛÂÈÚ¿ Û˘¯ÓfiÙËÙ·˜, ÛÙÔÓ ·ÚÈÛÙÂÚfi Ó‡ÌÔÓ· (45-51%), ÛÙÔÓ ‰ÂÍÈfi Ó‡ÌÔÓ· (29-35%) ‹ Î·È ÛÙÔ˘˜ ‰‡Ô
¡ÂÔÁÓÔÏÔÁÈ΋ ∫ÏÈÓÈ΋ ∞ÚÈÛÙÔÙ¤ÏÂÈÔ˘ ¶·ÓÂÈÛÙËÌ›Ô˘ £ÂÛ-
Û·ÏÔӛ΢, πÔÎÚ¿ÙÂÈÔ °¶¡ £ÂÛÛ·ÏÔӛ΢
Abstract: Congenital cystic adenomatoid malformation (CCAM) of the lung constitutes a rare but serious cause of neonatal respiratory distress. Three casesof histologically confirmed CCAM in newborn infants, two female and one male are reported. Two presented with respiratory distress immediately after birth and one at one month of age. In one case, the condition had been diagnosed prenatally. Postnatally, the diagnosis was made on the basis of the clinical features and the findings on radiological investigation (chest X-ray, computerized tomography). No other congenital anomalies were found. All three neonates underwent lobectomy shortly after diagnosis. The diagnosis was confirmed by histological examination, which revealed that two cases belonged to type 1 and one to type 4 CCAM. Two of the infants had a good outcome, whereasone died of sepsis in the immediate postoperative period.
Key words: adenomatoid malformation of the lung, congenital cysts
Ó‡ÌÔÓ˜ (2-14%) (2,3). ∏ ÚÒÙË ·ıÔÏÔÁÔ·Ó·ÙÔÌÈ΋ Ù·ÍÈÓfiÌËÛË Ù˘ ™∫∞¢¶ ¤ÁÈÓ ·fi ÙÔÓ Stocker (1977), Ô ÔÔ›Ô˜ ÌÂÏÂÙÒÓÙ·˜ 38 ÂÚÈÙÒÛÂȘ ™∫∞¢¶, ͯÒÚÈÛ 3 Ù‡Ô˘˜ (π-πππ), ·Ó¿ÏÔÁ· Ì ÙË ‰È¿ÌÂÙÚÔ ÙˆÓ Î‡ÛÙÂˆÓ Î·È ÙÔÓ Ù‡Ô ÙˆÓ Î˘ÙÙ¿ÚˆÓ Ô˘ ΢ÚÈ·Ú¯Ô‡Û·Ó ÛÙËÓ ÈÛÙÔÏÔÁÈ΋ ÂͤٷÛË: ÙÔÓ ÌÈÎÚÔ΢ÙÙ·ÚÈÎfi ‹ Ù‡Ô π (·ÛÙÂȘ <5 mm), ÙÔÓ ÂӉȿÌÂÛÔ ‹ Ù‡Ô ππ (·ÛÙÂȘ 0,5-2 cm) Î·È ÙÔÓ Ì·ÎÚÔ΢ÙÙ·ÚÈÎfi ‹ Ù‡Ô πππ
Department of Neonatology of Aristotelion University of Thessaloniki, “Ippokration”General Hospital, Thessaloniki
(·ÛÙÂȘ >2 cm) (4). ŸÏÔÈ ÔÈ ·Ú·¿Óˆ Ù‡ÔÈ ·ÓÙÈÛÙÔÈ¯Ô‡Û·Ó Û ‰˘ÛÏ·Û›· ÙÔ˘ ‚ÚÔÁ¯ÈÎÔ‡ ‰¤Ó‰ÚÔ˘, ·fi ÙÔ˘˜ ÌÂÁ¿ÏÔ˘˜ ‚ÚfiÁ¯Ô˘˜ ̤¯ÚÈ Ù· ÙÂÏÈο ‚ÚÔÁ¯ÈfiÏÈ· Î·È ÙÔ˘˜ ·ÂÚÒ‰ÂȘ Û¿ÎÔ˘˜, ÂÓÒ
¤ÏÂÈ·Ó ÙÂÏ›ˆ˜ ·ÛÙÂȘ ΢„ÂÏȉÈ΋˜ ÚÔ¤Ï¢Û˘.
∆Ô 1994, Ô Stocker ‰ËÌÔÛ›Â˘Û Ӥ· Ù·ÍÈÓfiÌËÛË, Ë
ÔÔ›· Û˘ÌÂÚÈÂÏ¿Ì‚·Ó 5 Ù‡Ô˘˜ (Ù‡ÔÈ 0-4) (¶›Ó·Î·˜ 1) (5). O Ù‡Ô˜ 0 Û˘Ó‰˘¿˙ÂÙ·È Ì ÛÔ‚·Ú¤˜ ‰È·Ì·Úٛ˜ ÙÔ˘ ΢ÎÏÔÊÔÚÈÎÔ‡ Î·È Â›Ó·È ·Û˘Ì‚›‚·ÛÙÔ˜ Ì ÙË ˙ˆ‹. O Ù‡Ô˜ 1 Â›Ó·È Ô Û˘¯ÓfiÙÂÚÔ˜ Ù‡Ô˜ Î·È Ô Ù‡Ô˜ 4 Ô Û·ÓÈfiÙÂÚÔ˜, ηıÒ˜ ·Ó·Ê¤ÚÔÓÙ·È ÛÙË ‰ÈÂıÓ‹ ‚È‚ÏÈÔÁÚ·Ê›· ÌfiÓÔ 3 ÙÂÎÌËÚȈ-
̤Ó˜ ÂÚÈÙÒÛÂȘ ™∫∞¢¶ Ù‡Ô˘ 4 (6,7). ™˘¯Ó¿ Ë
™∫∞¢¶, ȉȷ›ÙÂÚ· Ô Ù‡Ô˜ 2, Û˘Ó˘¿Ú¯ÂÈ Ì Ó¢ÌÔÓÈÎfi ·fiÏ˘ÌÌ· (8-10).
∏ ™∫∞¢¶ ÌÔÚ› Ó· ÂΉËψı› ÚÔÁÂÓÓËÙÈο
Ì ÔÏ˘-˘‰Ú¿ÌÓÈÔ Î·È ÌË ·ÓÔÛÔÏÔÁÈÎfi ‡‰Úˆ· (43%) Î·È Ó· ÚÔηϤÛÂÈ ÂÓ‰ÔÌ‹ÙÚÈÔ ı¿Ó·ÙÔ ‹ Ó· Ô‰ËÁ‹ÛÂÈ Û ÚfiˆÚÔ ÙÔÎÂÙfi (2,3). ªÂÙ¿ ÙË Á¤ÓÓËÛË, Ë ÓfiÛÔ˜ ÂΉËÏÒÓÂÙ·È Û˘Ó‹ıˆ˜ ÛÙË ÓÂÔÁÓÈ΋
ÂÚ›Ô‰Ô Î·È Ì¿ÏÈÛÙ· ÙȘ ÚÒÙ˜ ÒÚ˜ ÌÂÙ¿ ÙË Á¤ÓÓËÛË, Ì ·Ó·Ó¢ÛÙÈ΋ ‰˘Û¯¤ÚÂÈ·. ªÂÙ¿ ÙË ÓÂÔÁÓÈ΋ ÂÚ›Ô‰Ô, ÌÔÚ› Ó· ÂΉËψı› Ì ‚‹¯· Î·È ˘ÔÙÚÔÈ¿˙Ô˘Û˜ ÏÔÈÌÒÍÂȘ ÙÔ˘ ·Ó·Ó¢ÛÙÈÎÔ‡ ‹ Ó·
·Ú·Ì›ÓÂÈ ·Û˘Ìو̷ÙÈ΋ ÁÈ· ÔÏÏ¿ ¯ÚfiÓÈ· Î·È Ë ‰È¿ÁÓˆÛË Ó· Á›ÓÂÈ ·ÚÁfiÙÂÚ· ÛÙËÓ ÂÓ‹ÏÈÎË ˙ˆ‹ (1,11,12). ™˘¯Ó¿ Û˘Ó˘¿Ú¯Ô˘Ó Î·È ¿ÏϘ Û˘ÁÁÂÓ›˜ ·ÓˆÌ·Ï›Â˜ ·fi ÙÔÓ Ó‡ÌÔÓ· (Ó¢ÌÔÓÈÎfi ·fiÏ˘ÌÌ·) ‹ ·fi ¿ÏÏ· fiÚÁ·Ó·, fiˆ˜ Â›Ó·È ÔÈ ÓÂÊÚÔ› (ÓÂÊÚÈ΋ ·ÁÂÓÂÛ›·, ‰˘ÛÁÂÓÂÛ›·, ΢ÛÙÈ΋ ÓfiÛÔ˜ ÙˆÓ ÓÂÊÚÒÓ), Ë Î·Ú‰È¿, Ù· ÔÛÙ¿, ÙÔ ÎÂÓÙÚÈÎfi Ó¢ÚÈÎfi Û‡ÛÙËÌ· (˘‰Ú·ÓÂÁÎÂÊ·Ï›·, ˘‰ÚÔΤʷÏÔ˜) Î·È ÙÔ ¤ÓÙÂÚÔ (·ÙÚËÛ›·, Û˘ÁÁÂÓ‹˜ ‰È·ÊÚ·ÁÌ·ÙÔ΋ÏË) (2,3,10-12).
¶›Ó·Î·˜ 1. ¶·ıÔÏÔÁÔ·Ó·ÙÔÌÈÎÔ› Ù‡ÔÈ ™∫∞¢¶ (5)
¶ÂÚÈÁÚ¿ÊÔÓÙ·È ÙÚÂȘ ÂÚÈÙÒÛÂȘ ™∫∞¢¶ Û ÓÂÔÁÓ¿ Ô˘ ÓÔÛËχÙËÎ·Ó ÛÙËÓ ÎÏÈÓÈ΋ Ì·˜ Ù· ÙÂÏÂ˘Ù·›·
¯ÚfiÓÈ· Î·È Á›ÓÂÙ·È ·Ó·ÛÎfiËÛË Ù˘ ‚È‚ÏÈÔÁÚ·Ê›·˜.
¶ÂÚÈÁÚ·Ê‹ ÂÚÈÙÒÛˆÓ
¶ÂÚ›ÙˆÛË 1Ë
¡ÂÔÁÓfi ÎÔÚ›ÙÛÈ, Ì ËÏÈΛ· ·ËÛ˘ (∏∫) 36 ‚‰Ô-
Ì¿‰Â˜ Î·È ‚¿ÚÔ˜ Á¤ÓÓËÛ˘ (µ°) 3700 g, ‰È·ÎÔÌ›ÛÙËΠÛÙËÓ ÎÏÈÓÈ΋ ÙÔ 5Ô 24ˆÚÔ Ù˘ ˙ˆ‹˜ ÙÔ˘, ÁÈ·Ù› ·ÚÔ˘Û›·Û ·Ó·Ó¢ÛÙÈ΋ ‰˘Û¯¤ÚÂÈ· Ï›Á˜
ÒÚ˜ ÌÂÙ¿ ÙË Á¤ÓÓËÛË. ∆Ô ÎÏËÚÔÓÔÌÈÎfi ·Ó·ÌÓËÛÙÈ-
Îfi ‹Ù·Ó ÂχıÂÚÔ ÁÈ· ‰˘ÛϷۛ˜ Ó‡ÌÔÓ· ‹ Û˘Á-
ÁÂÓ›˜ ·ÛÙÂȘ ¿ÏÏˆÓ ÔÚÁ¿ÓˆÓ Î·È ‰ÂÓ ˘‹Ú¯Â
ÈÛÙÔÚÈÎfi ¤ÎıÂÛ˘ Û ‰˘ÓËÙÈο ÙÂÚ·ÙÔÁfiÓÔ˘˜ ·-
Ú¿ÁÔÓÙ˜ ηٿ ÙËÓ Î‡ËÛË. ∆Ô ˘ÂÚ˯ÔÁÚ¿ÊËÌ·
ÂÌ‚Ú‡Ô˘ ÙËÓ 20Ë Â‚‰ÔÌ¿‰· Ù˘ ·ËÛ˘ ‹Ù·Ó Ê˘-
ÛÈÔÏÔÁÈÎfi. ∫·Ù¿ ÙËÓ ÂÈÛ·ÁˆÁ‹ ÙÔ˘, Ë ·Ï‹ ·ÎÙÈÓÔÁÚ·Ê›· ıÒڷη ¤‰ÂÈÍ ¢ÌÂÁ¤ıË Î‡ÛÙË ÛÙÔ ‰ÂÍÈfi Ó¢ÌÔÓÈÎfi ‰›Ô, ¯ˆÚ›˜ ·ÚÂÎÙfiÈÛË ÙÔ˘ ÌÂÛÔıˆÚ·Î›Ô˘ (∂ÈÎfiÓ· 1). ¢ÂÓ ˘‹Ú¯·Ó ÂÌÊ·Ó›˜ ‰˘ÛϷۛ˜, ÂÓÒ Ô ˘ÂÚ˯ÔÁÚ·ÊÈÎfi˜ ¤ÏÂÁ¯Ô˜ ÂÁÎÂÊ¿ÏÔ˘, ηډȿ˜ Î·È ÓÂÊÚÒÓ ‹Ù·Ó Ê˘ÛÈÔÏÔÁÈÎfi˜. ∏ ·Ó·Ó¢ÛÙÈ΋ ‰˘Û¯¤ÚÂÈ· ·ÓÙÈÌÂÙˆ›ÛÙËΠ·Ú¯Èο
¯ÔÚ‹ÁËÛË Ô͢ÁfiÓÔ˘ Î·È ÙË 16Ë Ë̤ڷ ˙ˆ‹˜ ÙÔ
ÂͤٷÛË ‰È·ÈÛÙÒıËΠ̛· ¢ÌÂÁ¤ı˘ ·ÛÙË Ô˘ ÂÚÈ‚·ÏÏfiÙ·Ó ·fi ΢„ÂÏ›‰Â˜, ‚ÚfiÁ¯Ô˘˜ Î·È ‚ÚÔÁ¯ÈfiÏÈ· Î·È Î·Ï˘ÙfiÙ·Ó ·fi ΢ÏÈÓ‰ÚÈÎfi
ÎÚÔÛÛˆÙfi ÂÈı‹ÏÈÔ, Â˘Ú‹Ì·Ù· Û˘Ì‚·Ù¿ Ì ΢ÛÙÈ΋ ·‰Âӈ̷ÙÒ‰Ë ‰˘ÛÏ·Û›· ÙÔ˘ Ó‡ÌÔÓ· Ù‡Ô˘
1. ªÂÙ¿ ÙËÓ Â¤Ì‚·ÛË, ·Ú·ÙËÚ‹ıËΠηϋ ¤ÎÙ˘ÍË ÙÔ˘ Ó‡ÌÔÓ·, ·ÏÏ¿ ÙÔ ÓÂÔÁÓfi η٤ÏËÍ ÙËÓ 3Ë
ÌÂÙÂÁ¯ÂÈÚËÙÈ΋ Ë̤ڷ ·fi ÛË„·ÈÌ›·.
∆‡Ô˜ 0∆‡Ô˜ 1∆‡Ô˜ 2∆‡Ô˜ 3∆‡Ô˜ 4
™˘¯ÓfiÙËÙ· (%) 1-3>6520-2582-4
ª¤ÁÈÛÙÔ Ì¤ÁÂıÔ˜ ·ÛÙÂˆÓ (cm) 0,5102,527
ªÈÎÚÔÛÎÔÈ΋ ÂÌÊ¿ÓÈÛË ¢Ô̤˜ Ô˘¶ÔÏ˘ÏÔ‚Ò‰ÂȘ,ªÈÎÚ¤˜,™˘Ì·Á›˜, ¶ÔÏ˘ÏÔ‚Ò‰ÂȘ, ÌÔÈ¿˙Ô˘ÓÌÂÌÂÁ¿Ï˜ ·ÛÙÂȘÔÌÔÈfiÌÔÚʘ ÔÁÎÒ‰ÂȘÌÂÁ¿Ï˜ ‚ÚfiÁ¯Ô˘˜.Ì ÈÓÒ‰Ë Î‡ÛÙÂÈ˜Ô˘‚Ï¿‚˜ ÌÂÂÚÈÊÂÚÈΤ˜ ∫ÚÔÛÛˆÙfi,‰È·ÊÚ¿ÁÌ·Ù·.ÌÔÈ¿˙Ô˘Ó ÌÂÌÈÎÚ¤˜ ·ÛÙÂȘ. ΢ÏÈÓ‰ÚÈÎfi∫ÚÔÛÛˆÙfi ‰È·ÙÂٷ̤ӷ·ÂÚÔÊfiÚ˜∫˘„ÂÏȉÈο ·ÙÙ·Ú· ÂÈı‹ÏÈÔ ÌÂ΢ÏÈÓ‰ÚÈÎfiÙÂÏÈο ·ÛÙÂȘ.Ù‡Ô˘ π Î·Ï˘ÎÔÂȉ‹ ÂÈı‹ÏÈÔÌ ‚ÚÔÁ¯ÈfiÏÈ·.∫ÚÔÛÛˆÙfi, ·ÙÙ·Ú·‚ÏÂÓÓÔ·Ú·ÁˆÁ¿ ∫ÚÔÛÛˆÙfi ΢‚ÔÂȉ¤˜
·ÙÙ·Ú·Î˘‚ÔÂȉ¤˜ ‹ ÂÈı‹ÏÈÔ
΢ÏÈÓ‰ÚÈÎfi ÂÈı‹ÏÈÔ
ÃfiÓ‰ÚÔ˜ ¡·È5%-10% Ÿ¯ÈŸ¯ÈŸ¯È
ÙˆÓ ÂÚÈÙÒÛˆÓ
∂ÈÎfiÓ· 1. (¶ÂÚ›ÙˆÛË 1) ∂˘ÌÂÁ¤ı˘ ·ÛÙË ÛÙÔ ‰ÂÍÈfi Ó¢ÌÔ-
ÓÈÎfi ‰›Ô, ¯ˆÚ›˜ ·ÚÂÎÙfiÈÛË ÙÔ˘ ÌÂÛÔıˆÚ·Î›Ô˘.
¶ÂÚ›ÙˆÛË 2Ë
¡ÂÔÁÓfi ÎÔÚ›ÙÛÈ, Ì ∏∫ 36 ‚‰ÔÌ¿‰Â˜ Î·È µ°
2900 g, ‰È·ÎÔÌ›ÛÙËΠÛÙËÓ ÎÏÈÓÈ΋ ·Ì¤Ûˆ˜ ÌÂÙ¿ ÙË
Á¤ÓÓËÛË ÏfiÁˆ ‚·ÚÈ¿˜ ·Ó·Ó¢ÛÙÈ΋˜ ‰˘Û¯¤ÚÂÈ·˜.
∆Ô ÎÏËÚÔÓÔÌÈÎfi ·Ó·ÌÓËÛÙÈÎfi ‹Ù·Ó ÂχıÂÚÔ Î·È
‰ÂÓ ˘‹Ú¯Â ÁÓˆÛÙ‹ ¤ÎıÂÛË Û ÙÂÚ·ÙÔÁfiÓÔ˘˜ ·-
Ú¿ÁÔÓÙ˜ ηٿ ÙËÓ Î‡ËÛË. ™ÙÔ ˘ÂÚ˯ÔÁÚ¿ÊËÌ·
ÙÔ˘ ÂÌ‚Ú‡Ô˘ ›¯Â ‰È·ÁÓˆÛÙ› ·ÛÙË ÛÙÔ ‰ÂÍÈfi
Ó‡ÌÔÓ·, ¯ˆÚ›˜ ¿ÏÏ· ·ıÔÏÔÁÈο Â˘Ú‹Ì·Ù·. ∫·Ù¿
ÙËÓ ·ÓÙÈÎÂÈÌÂÓÈ΋ ÂͤٷÛË ‰ÂÓ ‰È·ÈÛÙÒıËÎ·Ó ÂÌ-
Ê·Ó›˜ Û˘ÁÁÂÓ›˜ ‰˘ÛϷۛ˜. ™ÙËÓ ·Ï‹ ·ÎÙÈÓÔ-
ÁÚ·Ê›· ıÒڷη ‰È·ÈÛÙÒıËΠ¢ÌÂÁ¤ı˘ ΢ÎÏÈ΋
·ÎÙÈÓԉȷʷӋ˜ ÂÚÈÔ¯‹ ÛÙÔ ‰ÂÍÈfi Ó‡ÌÔÓ·, ÂÚÈ‚·ÏÏfiÌÂÓË ·fi ·ÎÙÈÓÔÛÎÈÂÚfi ‰·ÎÙ‡ÏÈÔ (∂ÈÎfiÓ· 2·).
O ˘ÂÚ˯ÔÁÚ·ÊÈÎfi˜ ¤ÏÂÁ¯Ô˜ ÂÁÎÂÊ¿ÏÔ˘, ηډȿ˜ Î·È ÎÔÈÏÈ¿˜ ‹Ù·Ó Ê˘ÛÈÔÏÔÁÈÎfi˜. ∏ ·Ó·Ó¢ÛÙÈ΋ ‰˘Û¯¤ÚÂÈ· ·ÓÙÈÌÂÙˆ›ÛÙËΠ̠Ì˯·ÓÈÎfi ·ÂÚÈÛÌfi. ∆Ș ÂfiÌÂÓ˜ Ë̤Ú˜ ·Ú·ÙËÚ‹ıËΠ˘ÂÚ¤ÎÙ˘ÍË ÙÔ˘
‰ÂÍÈÔ‡ ¿Óˆ ÏÔ‚Ô‡ ÙÔ˘ Ó‡ÌÔÓ·, ÓÂ˘Ì·ÙÔ΋ÏË Î·È ·ÚÂÎÙfiÈÛË ÙÔ˘ ÌÂÛÔıˆÚ·Î›Ô˘ ÚÔ˜ Ù· ·ÚÈ-
ÛÙÂÚ¿ (∂ÈÎfiÓ· 2‚). ∆Ë 17Ë Ë̤ڷ ˙ˆ‹˜, ÙÔ ÓÂÔÁÓfi ˘Ô‚Ï‹ıËΠ۠ıˆÚ·ÎÔÙÔÌ‹ Î·È ÏÔ‚ÂÎÙÔÌ‹ ÙÔ˘ ‰ÂÍÈÔ‡ ¿Óˆ Î·È Ì¤ÛÔ˘ ÏÔ‚Ô‡. ™ÙËÓ ·ıÔÏÔÁÔ·Ó·ÙÔÌÈ΋ ÂͤٷÛË ‰È·ÈÛÙÒıËÎ·Ó Ì›· ¢ÌÂÁ¤ı˘ ·ÛÙË
ÛÙÔÓ ‰ÂÍÈfi ̤ÛÔ ÏÔ‚fi Î·È ‰‡Ô ÌÈÎÚfiÙÂÚ˜ ÛÙÔÓ ‰ÂÍÈfi ¿Óˆ ÏÔ‚fi, Ô˘ ÂÚÈ‚¿ÏÏÔÓÙ·Ó ·fi ΢„ÂÏ›‰Â˜
ÁÈ· 7 Ë̤Ú˜.
‰˘Û¯¤ÚÂÈ· ˘Ô¯ÒÚËÛ ÙÂÏ›ˆ˜ Î·È ÛÙËÓ ·ÎÙÈÓÔÁÚ·Ê›· ıÒڷη Ô Î¿Ùˆ ÏÔ‚fi˜ ÙÔ˘ ‰ÂÍÈÔ‡ Ó‡ÌÔÓ· ÂÎÙ‡¯ıËÎÂ Î·È Î·Ù¤Ï·‚ ÔÏfiÎÏËÚË ÙË ‰ÂÍÈ¿ ıˆÚ·ÎÈ΋ ÎÔÈÏfiÙËÙ· (∂ÈÎfiÓ· 2Á). ªÂÙ¿ ÙËÓ ¤ÍÔ‰Ô Î·È Ì¤¯ÚÈ ÙËÓ ËÏÈΛ· ÙˆÓ 4 ¯ÚfiÓˆÓ ‰ÂÓ ·ÚÔ˘Û›·Û ·Ó·Ó¢ÛÙÈο ÚÔ‚Ï‹Ì·Ù·.
¶ÂÚ›ÙˆÛË 3Ë
¡ÂÔÁÓfi ·ÁfiÚÈ, Ì ∏∫ 31 ‚‰ÔÌ¿‰Â˜ Î·È µ° 1620 g, ·ÚÔ˘Û›·Û ‹È· ·Ó·Ó¢ÛÙÈ΋ ‰˘Û¯¤ÚÂÈ· ·Ì¤Ûˆ˜ ÌÂÙ¿ ÙÔÓ ÙÔÎÂÙfi Î·È ‰È·ÎÔÌ›ÛÙËΠÛÙËÓ ÎÏÈÓÈ΋ ÙË 2Ë Ë̤ڷ ˙ˆ‹˜. ∏ ·ËÛË ‹Ù·Ó Ê˘ÛÈÔÏÔÁÈ΋, ÙÔ ÔÈÎÔÁÂÓÂÈ·Îfi ·Ó·ÌÓËÛÙÈÎfi ‹Ù·Ó ÂχıÂÚÔ Î·È ‰ÂÓ ·Ó·ÊÂÚfiÙ·Ó ¤ÎıÂÛË Û ÙÂÚ·ÙÔÁfiÓÔ˘˜ ·Ú¿ÁÔÓÙ˜. ™ÙË ‰È¿ÚÎÂÈ· Ù˘ ·ËÛ˘ ÁÈÓfiÙ·Ó Ù·ÎÙÈ΋ ·Ú·ÎÔÏÔ‡ıËÛË Ì ˘ÂÚ˯ÔÁÚ¿ÊËÌ· ÂÌ‚Ú‡Ô˘, ÛÙÔ ÔÔ›Ô ‰ÂÓ ‰È·ÈÛÙÒıËÎ·Ó Û˘ÁÁÂÓ›˜ ‰˘ÛϷۛ˜ ‹ ¿ÏÏ· ·ıÔÏÔÁÈο Â˘Ú‹Ì·Ù·. ∫·Ù¿ ÙËÓ ÂÈÛ·ÁˆÁ‹ ÙÔ˘, ‰ÂÓ ·ÚÔ˘Û›·˙ ‰˘ÛÌÔÚÊÈο ¯·Ú·ÎÙËÚÈÛÙÈο, Ô‡Ù ¿ÏϘ ÎÏÈÓÈΤ˜ ÂӉ›ÍÂȘ ‰˘ÛÌÔÚÊÈÎÔ‡ Û˘Ó‰ÚfiÌÔ˘. ™ÙËÓ ·Ï‹ ·ÎÙÈÓÔÁÚ·Ê›· ıÒڷη ‰È·ÈÛÙÒıËΠ‰È¿¯˘ÙË ‰ÈÎÙ˘ÔÎÔÎÎ҉˘ ·ÂÈÎfiÓÈÛË ÙˆÓ Ó¢ÌfiÓˆÓ Ì ·ÂÚÔ‚ÚÔÁ¯fiÁÚ·ÌÌ·, ‰›¯ˆ˜ ¿ÏÏ· ·ıÔÏÔÁÈο Â˘Ú‹Ì·Ù·. ∆¤ıËÎÂ Ë ‰È¿ÁÓˆÛË ÙÔ˘ Û˘Ó‰ÚfiÌÔ˘ ·Ó·Ó¢ÛÙÈ΋˜ ‰˘Û¯¤ÚÂÈ·˜ Î·È ·ÓÙÈÌÂÙˆ›ÛÙËΠ̠¯ÔÚ‹ÁËÛË Ì›·˜ ‰fiÛ˘ ÂÈÊ·ÓÂÈÔ‰Ú·ÛÙÈÎÔ‡ ·Ú¿ÁÔÓÙ· Î·È Ì˯·ÓÈÎfi ·ÂÚÈÛÌfi ÁÈ· 12 ÒÚ˜. ∏ ·Ó·Ó¢ÛÙÈ΋ ‰˘Û¯¤ÚÂÈ· ˘Ô¯ÒÚËÛ ÚÔԉ¢ÙÈο Î·È ÙÔ ÓÂÔÁÓfi ·Ú¤ÌÂÈÓ Û ηϋ ÁÂÓÈ΋ ηٿÛÙ·ÛË. ∆ËÓ 24Ë Ë̤ڷ Ù˘ ˙ˆ‹˜ ÙÔ˘ ·ÚÔ˘Û›·Û ÂÎ Ó¤Ô˘ ·ÈÊÓ›‰È· ·Ó·Ó¢ÛÙÈ΋ ‰˘Û¯¤ÚÂÈ·. ™Â ‰È·‰Ô¯ÈΤ˜ ·ÎÙÈÓÔÁڷʛ˜ ıÒڷη ÙȘ ÂfiÌÂÓ˜ Ë̤Ú˜ ·Ú·ÙËÚ‹ıËΠ‚·ıÌÈ·›· ˘Âڤ΢ÍË ÙÔ˘ ·ÚÈÛÙÂÚÔ‡ Ó‡ÌÔÓ· Ì ÔÏ˘Î˘ÛÙÈ΋ ·ÂÈÎfiÓÈÛË, ÌÂÙ·ÙfiÈÛË ÙÔ˘ ÌÂÛÔıˆÚ·Î›Ô˘ ‰ÂÍÈ¿ Î·È ·ÙÂÏÂÎÙ·Û›· ‰ÂÍÈÔ‡ Ó‡ÌÔÓ· (∂ÈÎfiÓ· 3·). ™ÙËÓ ·ÍÔÓÈ΋ ÙÔÌÔÁÚ·Ê›· ÙˆÓ Ó¢ÌfiÓˆÓ ‰È·ÈÛÙÒıËÎ·Ó ÔÏϷϤ˜ ·ÂÚÈÒ‰ÂȘ ÎÔÈÏfiÙËÙ˜ ÛÙÔÓ ·ÚÈÛÙÂÚfi ¿Óˆ ÏÔ‚fi, ·ÙÂÏÂÎÙ·Û›· ÂΠȤÛˆ˜ ÙÔ˘ ·ÚÈÛÙÂÚÔ‡ οو ÏÔ‚Ô‡, ÌÂÙ·ÙfiÈÛË ÌÂÛÔıˆÚ·Î›Ô˘ ÚÔ˜ Ù· ‰ÂÍÈ¿ Î·È ·ÙÂÏ‹˜ ¤ÎÙ˘ÍË ÙÔ˘ ‰ÂÍÈÔ‡ Ó‡ÌÔÓ· (∂ÈÎfiÓ· 3‚). ∆ËÓ 34Ë Ë̤ڷ Ù˘ ˙ˆ‹˜ ÙÔ˘, ÙÔ ÓÂÔÁÓfi ˘Ô‚Ï‹ıËΠ۠¯ÂÈÚÔ˘ÚÁÈ΋ ¤̂·ÛË, fiÔ˘ ¤ÁÈÓ ÂÎÙÔÌ‹ ÙÔ˘ ·ÚÈÛÙÂÚÔ‡ ¿Óˆ ÏÔ‚Ô‡ ÙÔ˘ Ó‡ÌÔÓ·. ™ÙËÓ ·ıÔÏÔÁÔ·Ó·ÙÔÌÈ΋ ÂͤٷÛË ‰È·ÈÛÙÒıËÎ·Ó ‰È¿Û·ÚÙ˜ ·ÛÙÂȘ ÛÙÔÓ ·ÚÈÛÙÂÚfi ÏÔ‚fi ÙÔ˘ Ó‡ÌÔÓ·, ·ÓÒÌ·Ï· ÂÚÈÁÂÁÚ·Ì̤Ó˜, Ô˘ ÂÚÈ‚¿ÏÏÔÓÙ·Ó ·fi ÏÂÙfi ÈÓÔÌ˘Ò‰Â˜ ÙÔ›¯ˆÌ· Î·È Î·Ï‡ÙÔÓÙ·Ó ·fi ·ÔÏ·Ù˘Ṳ̂ÓÔ ÌÔÓfiÛÙÈ‚Ô ÂÈı‹ÏÈÔ, Â˘Ú‹Ì·Ù· Û˘Ì‚·Ù¿ Ì ÙÔÓ Ù‡Ô 4 Ù˘ ™∫∞¢¶. ªÂÙ¿ ÙËÓ Â¤Ì‚·ÛË, ÙÔ ÓÂÔÁÓfi ·Ú¤ÌÂÈÓ Û Ì˯·ÓÈÎfi ·ÂÚÈÛÌfi ÁÈ· 5 Ë̤Ú˜. ∫ÏÈÓÈο, Ë ·Ó·Ó¢ÛÙÈ΋ ‰˘Û¯¤ÚÂÈ· ˘Ô¯ÒÚËÛ ÙÂÏ›ˆ˜ Î·È ÛÙÔÓ ·ÎÙÈÓÔÏÔÁÈÎfi ¤ÏÂÁ¯Ô ‰È·ÈÛÙÒıËΠÛÙ·‰È·Î‹ ¤ÎÙ˘ÍË ÙÔ˘
· ‚ Á
∂ÈÎfiÓ· 2. (¶ÂÚ›ÙˆÛË 2) ·) ∂˘ÌÂÁ¤ı˘ ΢ÎÏÈ΋ ·ÎÙÈÓԉȷʷӋ˜ ÂÚÈÔ¯‹ ÛÙÔ ‰ÂÍÈfi Ó‡ÌÔÓ·, ÂÚÈ‚·ÏÏfiÌÂÓË ·fi ·ÎÙÈÓÔÛÎÈÂÚfi ‰·ÎÙ‡ÏÈÔ. ‚) ªÂÙ¿ ÙËÓ ÂÊ·ÚÌÔÁ‹ Ì˯·ÓÈÎÔ‡ ·ÂÚÈÛÌÔ‡: ˘ÂÚ¤ÎÙ˘ÍË ÙÔ˘ ‰ÂÍÈÔ‡ ¿Óˆ ÏÔ‚Ô‡ ÙÔ˘ Ó‡ÌÔÓ·, ÓÂ˘Ì·ÙÔ΋ÏË Î·È ·ÚÂÎÙfiÈÛË ÙÔ˘ ÌÂÛÔıˆÚ·Î›Ô˘ ÚÔ˜ Ù· ·ÚÈÛÙÂÚ¿. Á) ªÂÙÂÁ¯ÂÈÚËÙÈο: ¤ÎÙ˘ÍË ÙÔ˘ οو ÏÔ‚Ô‡ ÙÔ˘ ‰ÂÍÈÔ‡ Ó‡ÌÔÓ·, Ô ÔÔ›Ô˜ η٤Ϸ‚ ÔÏfiÎÏËÚË ÙË ‰ÂÍÈ¿ ıˆÚ·ÎÈ΋ ÎÔÈÏfiÙËÙ·.
∂ÈÎfiÓ· 3. (¶ÂÚ›ÙˆÛË 3) ·) ÀÂڤ΢ÍË ÙÔ˘ ·ÚÈÛÙÂÚÔ‡ Ó‡ÌÔÓ· Ì ÔÏ˘Î˘ÛÙÈ΋ ·ÂÈÎfiÓÈÛË, ÌÂÙ·ÙfiÈÛË ÙÔ˘ ÌÂÛÔıˆÚ·Î›Ô˘ ‰ÂÍÈ¿ Î·È ·ÙÂÏÂÎÙ·Û›· ‰ÂÍÈÔ‡ Ó‡ÌÔÓ·. ‚) ∞ÍÔÓÈ΋ ÙÔÌÔÁÚ·Ê›· ÙˆÓ Ó¢ÌfiÓˆÓ: ÔÏϷϤ˜ ·ÂÚÈÒ‰ÂȘ ÎÔÈÏfiÙËÙ˜ ÛÙÔÓ ·ÚÈÛÙÂÚfi ¿Óˆ ÏÔ‚fi, ·ÙÂÏÂÎÙ·Û›· ÂΠȤÛˆ˜ ÙÔ˘ ·ÚÈÛÙÂÚÔ‡ οو ÏÔ‚Ô‡, ÌÂÙ·ÙfiÈÛË ÌÂÛÔıˆÚ·Î›Ô˘ ÚÔ˜ Ù· ‰ÂÍÈ¿ Î·È ·ÙÂÏ‹˜ ¤ÎÙ˘ÍË ÙÔ˘
‰ÂÍÈÔ‡ Ó‡ÌÔÓ·. Á) ªÂÙÂÁ¯ÂÈÚËÙÈο: ¤ÎÙ˘ÍË ÙÔ˘ ·ÚÈÛÙÂÚÔ‡ οو ÏÔ‚Ô‡ Î·È Î·Ù¿ÏË„Ë Ù˘ ·ÚÈÛÙÂÚ‹˜ ıˆÚ·ÎÈ΋˜ ÎÔÈÏfiÙËÙ·˜. ¢È·ÎÚ›ÓÂÙ·È Ë ·ÚÔ˘Û›· ıˆÚ·ÎÈ΋˜·ÚÔ¯¤Ù¢Û˘. · ‚ Á
Î·È Î·Ù¿ÏË„Ë Ù˘ ·ÚÈÛÙÂÚ‹˜ ıˆÚ·ÎÈ΋˜ ÎÔÈÏfiÙËÙ·˜ (∂ÈÎfiÓ· 3Á). ªÂÙ¿ ÙËÓ ¤ÍÔ‰Ô ·fi ÙËÓ ÎÏÈÓÈ΋
Î·È Ì¤¯ÚÈ ÙËÓ ËÏÈΛ· ÙˆÓ 8 ÌËÓÒÓ, ‰ÂÓ ·ÚÔ˘Û›·Û ·Ó·Ó¢ÛÙÈο ÚÔ‚Ï‹Ì·Ù·.
™˘˙‹ÙËÛË
OÈ ÂÚÈÙÒÛÂȘ ™∫∞¢¶ Ô˘ ÂÚÈÁÚ¿ÊÔ˘Ì ¤¯Ô˘Ó Ù· ÂÍ‹˜ ¯·Ú·ÎÙËÚÈÛÙÈο: ·) Û ̛· ÌfiÓÔ ÂÚ›ÙˆÛË ˘‹Ú¯Â ÚÔÁÂÓÓËÙÈ΋ ‰È¿ÁÓˆÛË, ·Ó Î·È ˘ÂÚ˯ÔÁÚ¿ÊËÌ· ÂÌ‚Ú‡Ô˘ ¤ÁÈÓ Û fiϘ ÙȘ ÂÚÈÙÒÛÂȘ, ‚) fiϘ ÂΉËÏÒıËÎ·Ó ÛÙË ÓÂÔÁÓÈ΋ ËÏÈΛ·, Á) Û η̛· ‰ÂÓ ˘‹Ú¯·Ó ‰˘ÛϷۛ˜ ¿ÏÏˆÓ ÔÚÁ¿ÓˆÓ Î·È ‰) ÔÈ ‰‡Ô ÂÚÈÙÒÛÂȘ ‹Ù·Ó Ù‡Ô˘ 1 Î·È Ë Ì›· Ù‡Ô˘ 4. ∏ ·ıÔÁ¤ÓÂÈ· Ù˘ ™∫∞¢¶ ‰ÂÓ Â›Ó·È Ï‹Úˆ˜ ÁÓˆÛÙ‹. Œ¯ÂÈ ıˆÚËı› ˆ˜ ·Ì¿Úو̷, ÂÓÙÔÈṲ̂ÓË ‰˘ÛÏ·Û›· ÙÔ˘ Ó‡ÌÔÓ· Î·È ·Ó·Ù˘Íȷ΋ ‰È·Ù·Ú·¯‹ (12). ∏ Û˘¯Ó‹ Û˘Ó‡·ÚÍË Ó¢ÌÔÓÈÎÔ‡ ·ÔχÌÌ·ÙÔ˜ ÂÓÈÛ¯‡ÂÈ ÙËÓ ¿Ô„Ë Ù˘ ·Ó·Ù˘ÍÈ·-
΋˜ ‰È·Ù·Ú·¯‹˜. ¶Ôχ ÚfiÛÊ·Ù·, ÔÈ MÔrotti Î·È Û˘Ó, ¯ÚËÛÈÌÔÔÈÒÓÙ·˜ ·ÓÔÛÔ˚ÛÙÔ¯ËÌÈΤ˜ ÌÂıfi‰Ô˘˜, ÌÂϤÙËÛ·Ó ÙÔÓ Ù‡Ô ÙˆÓ Î˘ÙÙ¿ÚˆÓ 22 ÂÚÈÙÒÛÂˆÓ ™∫∞¢¶ Î·È ÙÔÓ Û˘Û¯¤ÙÈÛ·Ó Ì ÙËÓ ·ıÔÁ¤ÓÂÈ· Ù˘ ÓfiÛÔ˘ (6,13). ∫·Ù¤ÏËÍ·Ó ÛÙÔ Û˘Ì¤Ú·ÛÌ· fiÙÈ Ë ÓfiÛÔ˜ ÔÊ›ÏÂÙ·È Û ·Ó·ÛÙÔÏ‹ Ù˘ ·Ó¿Ù˘Í˘ ÙˆÓ Ó¢ÌfiÓˆÓ Û ‰È·ÊÔÚÂÙÈΤ˜ Ê¿ÛÂȘ Ù˘ ÂͤÏÈ͢ ÙÔ˘ ÙÚ·¯ÂÈÔ‚ÚÔÁ¯ÈÎÔ‡ ‰¤Ó‰ÚÔ˘. ŒÙÛÈ, ÔÈ Ù‡ÔÈ 1 ¤ˆ˜ 3 ÚÔ·ÙÔ˘Ó ·fi ·Ó·ÛÙÔÏ‹ Ù˘
Ó¢ÌÔÓÈ΋˜ ·Ó¿Ù˘Í˘ ηٿ ÙË Ê¿ÛË Ù˘ ·Ó¿Ù˘Í˘ ÙˆÓ ‚ÚfiÁ¯ˆÓ ̤¯ÚÈ Ù· ÙÂÏÈο ‚ÚÔÁ¯ÈfiÏÈ· (pseudocanalicular stage) Î·È ÔÈ Î‡ÛÙÂȘ ηχÙÔÓÙ·È ·fi ÂÈı‹ÏÈÔ ‚ÚÔÁ¯ÈÎÔ‡ Ù‡Ô˘. O Ù‡Ô˜ 4 ÔÊ›ÏÂÙ·È Û ·Ó·ÛÙÔÏ‹ Ù˘ ·Ó¿Ù˘Í˘ ÙˆÓ Î˘„ÂÏ›‰ˆÓ (saccular stage) Î·È ÔÈ Î‡ÛÙÂȘ ·ÚÔ˘ÛÈ¿˙Ô˘Ó ÂÈı‹ÏÈÔ Î˘„ÂÏȉÈÎÔ‡ Ù‡Ô˘ (6,13).
∏ ™∫∞¢¶ ÌÔÚ› Ó· ‰È·ÁÓˆÛÙ› Ì ÙÔ ˘ÂÚ˯ÔÁÚ¿ÊËÌ· ÙÔ˘ ÂÌ‚Ú‡Ô˘ ·fi ÙË 17Ë Â‚‰ÔÌ¿‰· Ù˘ ·ËÛ˘ (3,12,14-16). ªÂ ‚¿ÛË Ù· ˘ÂÚ˯ÔÁÚ·ÊÈο
‰È¿ÁÓˆÛË ™∫∞¢¶ (11) ∞Û˘Ìو̷ÙÈο ÓÂÔÁÓ¿™˘Ìو̷ÙÈο* ÓÂÔÁÓ¿
∞/· ıÒڷη ÛÙË Á¤ÓÓËÛË∞/· ıÒڷη + CT ÛÙË Á¤ÓÓËÛË
∞ÚÓËÙÈ΋∞ÌÊ›‚ÔÏË£ÂÙÈ΋∞ÚÓËÙÈ΋
CT (6Ô Ì‹Ó·)CT (Á¤ÓÓËÛË)ÃÂÈÚÔ˘ÚÁ›Ô∂·ÓÂÎÙ›ÌËÛË
∞ÚÓËÙÈ΋£ÂÙÈ΋∞ÚÓËÙÈ΋£ÂÙÈ΋
⁄ÊÂÛËÃÂÈÚÔ˘ÚÁ›Ô∂·ÓÂÎÙ›ÌËÛËÃÂÈÚÔ˘ÚÁ›Ô** (6Ô Ì‹Ó·)
CT:·ÍÔÓÈ΋ ÙÔÌÔÁÚ·Ê›· ıÒڷη * ·Ó·Ó¢ÛÙÈ΋ ‰˘Û¯¤ÚÂÈ· **Ë ¯ÂÈÚÔ˘ÚÁÈ΋ ·ÓÙÈÌÂÙÒÈÛË ÌÔÚ› Ó· ηı˘ÛÙÂÚ‹ÛÂÈ Ì¤¯ÚÈ ÙÔÓ 6Ô Ì‹Ó· Ù˘ ˙ˆ‹˜
Â˘Ú‹Ì·Ù·, ‰È·ÎÚ›ÓÔÓÙ·È ‰‡Ô Ù‡ÔÈ, Ô Ì·ÎÚÔ΢ÙÙ·-
ÚÈÎfi˜ Î·È Ô ÌÈÎÚÔ΢ÙÙ·ÚÈÎfi˜ (3,17), ¯ˆÚ›˜ fï˜ Ó· ˘¿Ú¯ÂÈ ·ÓÙÈÛÙÔȯ›· Ì ÙÔ˘˜ ·ıÔÏÔÁÔ·Ó·ÙÔÌÈÎÔ‡˜
Ù‡Ô˘˜ Ù˘ ÓfiÛÔ˘, Ô˘ ÂÚÈÁÚ¿ÊËÎ·Ó ·fi ÙÔÓ
Stocker (2). ∆Ô ˘ÂÚ˯ÔÁÚ¿ÊËÌ· ÙÔ˘ ÂÌ‚Ú‡Ô˘ Â›Ó·È ÛËÌ·ÓÙÈÎfi fi¯È ÌfiÓÔ ÁÈ· ÙËÓ ÚÔÁÂÓÓËÙÈ΋ ‰È¿-
ÁÓˆÛË, ·ÏÏ¿ Î·È ÁÈ· ÙËÓ ·Ú·ÎÔÏÔ‡ıËÛË Ù˘ ‚Ï¿‚˘ Î·È ÙËÓ ÚfiÁÓˆÛË. ∞fi Ù· Â˘Ú‹Ì·Ù· ÙÔ˘ ˘Â-
Ú˯ÔÁÚ·Ê‹Ì·ÙÔ˜ ÙÔ˘ ÂÌ‚Ú‡Ô˘, Ë ÌÈÎÚÔ΢ÛÙÈ΋ ‹ ·ÌÊÔÙÂÚfiÏ¢ÚË ÂÌÊ¿ÓÈÛË ÙˆÓ ‚Ï·‚ÒÓ, ÙÔ ÔÏ˘˘‰Ú¿ÌÓÈÔ, Ô ÂÌ‚Ú˘˚Îfi˜ ‡‰Úˆ·˜ Î·È Ë ÌÂÙ·ÙfiÈÛË
ÙÔ˘ ÌÂÛÔıˆÚ·Î›Ô˘ ·ÔÙÂÏÔ‡Ó ‰˘ÛÌÂÓ›˜ ÚÔÁÓˆ-
ÛÙÈÎÔ‡˜ ·Ú¿ÁÔÓÙ˜ (1-3,11,15,17,18). øÛÙfiÛÔ, Ë
ÚÔÁÂÓÓËÙÈ΋ ηıÔ‰‹ÁËÛË Ú¤ÂÈ Ó· Á›ÓÂÙ·È Ì ÌÂ-
Á¿ÏË ÚÔÛÔ¯‹, ÁÈ·Ù› ˘¿Ú¯ÂÈ ÛËÌ·ÓÙÈÎfi ÔÛÔÛÙfi
Ï·Óı·Ṳ̂Ó˘ ‰È¿ÁÓˆÛ˘ ‹ ·˘ÙfiÌ·Ù˘ ‡ÊÂÛ˘. OÈ McCullagh Î·È Û˘Ó ·Ú·ÎÔÏÔ‡ıËÛ·Ó ÁÈ· ‰È¿ÛÙËÌ·
25 ÌËÓÒÓ 13 ÂÚÈÙÒÛÂȘ Ì ÚÔÁÂÓÓËÙÈ΋ ‰È¿ÁÓˆ-
ÛË ™∫∞¢¶ Î·È ‰È·›ÛÙˆÛ·Ó fiÙÈ Ë ÓfiÛÔ˜ ÂȂ‚·ÈÒıËΠÌfiÓÔ ÛÙÔ 54% (16). ∂ÈϤÔÓ, ÔÈ Laberge Î·È Û˘Ó, Û ÔÏ˘ÎÂÓÙÚÈ΋ ÌÂϤÙË 48 ÂÚÈÙÒÛÂˆÓ ÌÂ
ÚÔÁÂÓÓËÙÈ΋ ‰È¿ÁÓˆÛË ™∫∞¢¶, ‚Ú‹Î·Ó fiÙÈ ÛÙÔ 56% ÔÈ Î‡ÛÙÂȘ ˘Ô¯ÒÚËÛ·Ó ÛËÌ·ÓÙÈο Û ̤ÁÂıÔ˜
‹ ÂÍ·Ê·Ó›ÛÙËÎ·Ó Ì¤¯ÚÈ ÙË Á¤ÓÓËÛË (1). ∫·È ¿ÏÏÔÈ
Û˘ÁÁÚ·Ê›˜ ·Ó·Ê¤ÚÔ˘Ó ·˘ÙfiÌ·ÙË ÛÌ›ÎÚ˘ÓÛË ‹ ÂÍ·Ê¿ÓÈÛË ÙˆÓ Î‡ÛÙÂˆÓ Ô˘ ‰È·ÁÓÒÛÙËÎ·Ó ÚÔÁÂÓÓËÙÈο, Û ÔÛÔÛÙ¿ Ô˘ Î˘Ì·›ÓÔÓÙ·È ·fi 18% ̤¯ÚÈ 85% (10,11,15,19). °È’ ·˘Ùfi, ÛÙȘ ÂÚÈÛÛfiÙÂÚ˜ ÂÚÈÙÒÛÂȘ ÚÔÁÂÓÓËÙÈ΋˜ ‰È¿ÁÓˆÛ˘ ™∫∞¢¶ Û˘ÓÈÛÙ¿Ù·È ·Ú·ÎÔÏÔ‡ıËÛË ÙÔ˘ ÂÌ‚Ú‡Ô˘ Î·È Û˘ÓÙËÚËÙÈ΋ ·ÓÙÈÌÂÙÒÈÛË (1,10,19). ™·Ê‹ ¤Ó‰ÂÈÍË ÂÓ‰ÔÌ‹ÙÚÈ·˜ ¯ÂÈÚÔ˘ÚÁÈ΋˜ ·ÓÙÈÌÂÙÒÈÛ˘, Ë ÔÔ›·
Û˘Ó›ÛÙ·Ù·È Û ıˆÚ·ÎÔ·ÌÓȷ΋ ·ÚÔ¯¤Ù¢ÛË ‹ ÏÔ-
‚ÂÎÙÔÌ‹, ·ÔÙÂÏ› Ô ÂÌ‚Ú˘˚Îfi˜ ‡‰Úˆ·˜ (1,10,20).
ªÂÙ¿ ÙË Á¤ÓÓËÛË, Ë ™∫∞¢¶ ÂΉËÏÒÓÂÙ·È Û˘Ó‹ıˆ˜ ÙÔÓ ÚÒÙÔ Ì‹Ó· Ù˘ ˙ˆ‹˜ Ì ·Ó·Ó¢ÛÙÈ΋ ‰˘Û¯¤ÚÂÈ· (21,15), ÁÈ· ÙËÓ ÔÔ›· ÌÔÚ› Ó· ¯ÚÂÈ·ÛÙ› Ì˯·ÓÈÎfi˜ ·ÂÚÈÛÌfi˜, Û˘Ì‚·ÙÈÎfi˜ ‹ ˘„›Û˘¯ÓÔ˜, fiˆ˜ ÛÙȘ ÂÚÈÙÒÛÂȘ Ù˘ ·ÚÔ‡Û·˜ ÌÂϤÙ˘ (2,11,12,15,21). ∂›Û˘, Ë ÚÔԉ¢ÙÈ΋ ‰È¿Ù·ÛË ÙˆÓ Î‡ÛÙÂˆÓ Â›Ó·È ‰˘Ó·ÙfiÓ, ›Ù ·˘ÙfiÌ·Ù· ›Ù ÏfiÁˆ ÂÊ·ÚÌÔÁ‹˜ ıÂÙÈÎÒÓ È¤ÛˆÓ, Ó· ÚÔηϤÛÂÈ ·ÙÂÏÂÎÙ·Û›· ÛÙÔ Á‡Úˆ Ó¢ÌÔÓÈÎfi ·Ú¤Á¯˘Ì·, ·ÚÂÎÙfiÈÛË ÙÔ˘ ÌÂÛÔıˆÚ·Î›Ô˘ Î·È ›ÂÛË ÙˆÓ Ê˘ÛÈÔÏÔÁÈÎÒÓ ÏÔ‚ÒÓ ÙÔ˘ Ó‡ÌÔÓ·, Ô˘ Ô‰ËÁÔ‡Ó Û ·ÈÊÓ›‰È· Âȉ›ӈÛË Ù˘ ·Ó·Ó¢ÛÙÈ΋˜ ‰˘Û¯¤ÚÂÈ·˜, fiˆ˜ Û˘Ó¤‚Ë ÛÙË 2Ë Î·È 3Ë ÂÚ›ÙˆÛË. ™Â fiϘ ÙȘ ÂÚÈÙÒÛÂȘ Ù˘ ·ÚÔ‡Û·˜ ÌÂϤÙ˘, Ë ‰È¿ÁÓˆÛË Ù˘ ÓfiÛÔ˘ ‚·Û›ÛÙËΠÛÙ· Â˘Ú‹Ì·Ù· Ù˘ ·ÎÙÈÓÔÁÚ·Ê›·˜ ıÒڷη, fiÔ˘ ‰È·ÈÛÙÒıËÎ·Ó Î‡ÛÙÂȘ ÔÈΛÏÔ˘ ÌÂÁ¤ıÔ˘˜ ÁÂÌ¿Ù˜ Ì ·¤Ú·. ™·ÓÈfiÙÂÚ·, ÔÈ ÌÈÎÚÔ΢ÛÙÈΤ˜ ‚Ï¿‚˜ (Ù‡Ô˜ 3) ÌÔÚ› Ó· ÂÌÊ·Ó›˙ÔÓÙ·È ˆ˜ ÎÔÎÎÈÒ‰ÂȘ ‹ Û˘Ì·Á›˜ ‚Ï¿‚˜ (12). ∏ ·ÍÔÓÈ΋ ÙÔÌÔÁÚ·Ê›· ÂȂ‚·ÈÒÓÂÈ ÙË ‰È¿ÁÓˆÛË Î·È ·ÔηχÙÂÈ ÙËÓ ¤ÎÙ·ÛË Ù˘ ‚Ï¿‚˘ (12). ¶Ú¤ÂÈ Ó· Á›ÓÂÙ·È Î·È ÛÙȘ ÂÚÈÙÒÛÂȘ fiÔ˘ Ë ÂÓ‰ÔÌ‹ÙÚÈ· ·Ú·ÎÔÏÔ‡ıËÛË ¤‰ÂÈÍ ÛÌ›ÎÚ˘ÓÛË ‹ ÂÍ·Ê¿ÓÈÛË ÙˆÓ Î‡ÛÙˆÓ, ÁÈ·Ù› ÛÙȘ ÂÚÈÙÒÛÂȘ ·˘Ù¤˜ ˘¿Ú¯Ô˘Ó ‚Ï¿‚˜ Ô˘ ‰ÂÓ Â›Ó·È ÂÌÊ·Ó›˜ ÛÙËÓ ·Ï‹ ·ÎÙÈÓÔÁÚ·Ê›· ÙÔ˘ ıÒڷη Î·È ·Ô‰ÂÈÎÓ‡ÔÓÙ·È ÌfiÓÔ Ì ÙËÓ ·ÍÔÓÈ΋ ÙÔÌÔÁÚ·Ê›· Ó‡ÌÔÓ· (9). O ¯ÚfiÓÔ˜ Ù˘ ¯ÂÈÚÔ˘ÚÁÈ΋˜ ·ÓÙÈÌÂÙÒÈÛ˘ ÂÍ·ÚÙ¿Ù·È ·fi ÙËÓ ·ÚÔ˘Û›· Û˘ÌÙˆÌ¿ÙˆÓ ·fi ÙÔ ·Ó·Ó¢ÛÙÈÎfi. ∆· Û˘Ìو̷ÙÈο ÓÂÔÁÓ¿ Ì ™∫∞¢¶ ˘Ô‚¿ÏÏÔÓÙ·È ÁÚ‹ÁÔÚ· ÌÂÙ¿ ÙË Á¤ÓÓËÛË Û ¯ÂÈÚÔ˘ÚÁÈ΋ ¤̂·ÛË, Ë ÔÔ›· Û˘Ó›ÛÙ·Ù·È Û ÏÔ‚ÂÎÙÔÌ‹ ‹ ÙÌËÌ·ÙÂÎÙÔÌ‹ (11,12,15). °È· Ù· ·Û˘Ìو̷ÙÈο ÓÂÔÁÓ¿, ÔÚÈṲ̂ÓÔÈ ˘ÔÛÙËÚ›˙Ô˘Ó fiÙÈ ı· Ú¤ÂÈ Ó· ¯ÂÈÚÔ˘ÚÁÔ‡ÓÙ·È ·Ì¤Ûˆ˜ ÌÂÙ¿ ÙË Á¤ÓÓËÛË (22,23), ÂÓÒ ¿ÏÏÔÈ ÚÔÙ›ÓÔ˘Ó
¯ÂÈÚÔ˘ÚÁÈ΋ ·ÓÙÈÌÂÙÒÈÛË ·ÚÁfiÙÂÚ·, ÌÂÙ¿ ÙËÓ ËÏÈΛ· ÙˆÓ 6 ÌËÓÒÓ (11). O ÚÔÙÂÈÓfiÌÂÓÔ˜ ·ÏÁfiÚÈıÌÔ˜ ÁÈ· ÙË ıÂڷ¢ÙÈ΋ ·ÓÙÈÌÂÙÒÈÛË ÓÂÔÁÓÒÓ Ì ÚÔÁÂÓÓËÙÈ΋ ‰È¿ÁÓˆÛË ™∫∞¢¶ Ê·›ÓÂÙ·È ÛÙÔÓ ¶›Ó·Î·
2. ¶¿ÓÙˆ˜, fiÛÔÓ ·ÊÔÚ¿ ÛÙËÓ ·fiÊ·ÛË ÁÈ· ÙÔ ¯ÚfiÓÔ Ù˘ ¤̂·Û˘, Ú¤ÂÈ Ó· Ï·Ì‚¿ÓÔÓÙ·È ˘’ fi„ÈÓ
ÔÈ Î›Ó‰˘ÓÔÈ ·fi ÙËÓ Î·ı˘ÛÙÂÚË̤ÓË ·Ê·›ÚÂÛË Ù˘
‚Ï¿‚˘, fiˆ˜ Â›Ó·È Ë Û˘Ì›ÂÛË ÙˆÓ Ó¢ÌfiÓˆÓ, ÔÈ
ÏÔÈÌÒÍÂȘ, ·ÎfiÌË Î·È Ë Èı·ÓfiÙËÙ· ηÎÔ‹ıÔ˘˜
ÂÍ·ÏÏ·Á‹˜ Ù˘ ‚Ï¿‚˘ (22-25).
∏ ÚfiÁÓˆÛË Ù˘ ™∫∞¢¶ Â›Ó·È Î·Ï‹ ÁÈ· ÙÔÓ Ù‡Ô 1 Î·È ÊÙˆ¯‹ ÁÈ· ÙÔ˘˜ Ù‡Ô˘˜ 2 Î·È 3, ÂÓÒ ‰ÂÓ ˘¿Ú¯Ô˘Ó ‚È‚ÏÈÔÁÚ·ÊÈο ‰Â‰Ô̤ӷ ÁÈ· ÙÔÓ Ù‡Ô 4 (1). OÈ ÓÂÔÁÓÈÎÔ› ı¿Ó·ÙÔÈ ÔÊ›ÏÔÓÙ·È Î˘Ú›ˆ˜ ÛÙËÓ
Ó¢ÌÔÓÈ΋ ˘ÔÏ·Û›· ‹ ÛÙȘ ÛÔ‚·Ú¤˜ Û˘ÁÁÂÓ›˜ ·ÓˆÌ·Ï›Â˜ Ô˘ Û˘Ó˘¿Ú¯Ô˘Ó (1,10,21). ∏ Û˘¯ÓfiÙËÙ· Û˘ÁÁÂÓÒÓ ‰È·Ì·ÚÙÈÒÓ Â›Ó·È ÌÂÁ¿ÏË ÛÙË
™∫∞¢¶ Ù‡Ô˘ 2, ÂÚ›Ô˘ 20% (7-50%) Î·È ÌÈÎÚfiÙÂÚË ÛÙÔÓ Ù‡Ô 1 (5-12,5%) (4,5,8,12). °È· ÙÔÓ Ù‡Ô 4 ‰ÂÓ Â›Ó·È ÁÓˆÛÙ‹ Ë Û˘¯ÓfiÙËÙ· Û˘Ó˘·Ú¯fiÓÙˆÓ
Û˘ÁÁÂÓÒÓ ‰È·Ì·ÚÙÈÒÓ. ™Â Ì›· ÌfiÓÔ ·fi ÙȘ ‰ËÌÔÛÈÂ˘Ì¤Ó˜ ÂÚÈÙÒÛÂȘ ·Ó·Ê¤ÚÂÙ·È Û·ÊÒ˜ fiÙÈ ‰ÂÓ ˘‹Ú¯·Ó ¿ÏϘ ‰˘ÛϷۛ˜ (7). ™ÙËÓ ÂÚ›ÙˆÛË
™∫∞¢¶ Ù‡Ô˘ 4 Ô˘ ÂÚÈÁÚ¿ÊËÎÂ, ‰ÂÓ ˘‹Ú¯·Ó ‰˘ÛϷۛ˜ ¿ÏÏˆÓ ÔÚÁ¿ÓˆÓ Î·È Ë ¤Î‚·ÛË ‹Ù·Ó ηϋ. ∞Ó·ÊÔÚÈο Ì ÙË Ì·ÎÚÔ¯ÚfiÓÈ· ÚfiÁÓˆÛË ·È‰ÈÒÓ Ì ™∫∞¢¶ Ô˘ ˘Ô‚¿ÏÏÔÓÙ·È Û ¯ÂÈÚÔ˘ÚÁÈ΋ ¤̂·ÛË, ·˘Ù‹ Â›Ó·È Î·Ï‹, ηıÒ˜ ÌÂÙ¿ ·fi ÙË ÏÔ‚ÂÎÙÔÌ‹ ‚ÂÏÙÈÒÓÂÙ·È Ë Ó¢ÌÔÓÈ΋ ÏÂÈÙÔ˘ÚÁ›·, ·Ú¿ Ù· ‹È· ·ÎÙÈÓÔÏÔÁÈο Â˘Ú‹Ì·Ù· Ô˘ ÌÔÚ› Ó· ˘¿Ú¯Ô˘Ó, fiˆ˜ Â›Ó·È ÙÔ ·ÓÙÈÛÙ·ıÌÈÛÙÈÎfi ÂÌʇÛËÌ· (26). ™Ô‚·Ú‹ ÂÈÏÔ΋ Ì·ÎÚÔÚfiıÂÛÌ· ·ÔÙÂÏ› Ë “˘ÔÏÂÈÌÌ·ÙÈ΋” ™∫∞¢¶, ‰ËÏ·‰‹ Ë fi„ÈÌË ÂÌÊ¿ÓÈÛË Û˘ÌÙˆÌ¿ÙˆÓ Ô˘ ÔÊ›ÏÔÓÙ·È Û ÌÈÎÚÔ΢ÛÙÈΤ˜ ‚Ï¿‚˜, ÔÈ Ôԛ˜ ‰ÂÓ ¤ÁÈÓ·Ó ·ÓÙÈÏËÙ¤˜ ÛÙÔÓ ·Ú¯ÈÎfi ¤ÏÂÁ¯Ô ηÈ, ηٿ Û˘Ó¤ÂÈ·, ‰ÂÓ ·Ê·ÈÚ¤ıËÎ·Ó Ì ÙËÓ ·Ú¯È΋ ¤̂·ÛË (26). OÈ ‰‡Ô ·ÛıÂÓ›˜ Ô˘ ¤˙ËÛ·Ó ÌÂÙ¿ ÙË ÓÂÔÁÓÈ΋ ÂÚ›Ô‰Ô, Û‹ÌÂÚ· ËÏÈΛ·˜ 4 ÂÙÒÓ Î·È 8 ÌËÓÒÓ ·ÓÙ›ÛÙÔȯ·, ‰ÂÓ ·ÚÔ˘Û›·Û·Ó ·Ó·Ó¢ÛÙÈο ÚÔ‚Ï‹Ì·Ù·. ™˘ÌÂÚ·ÛÌ·ÙÈο, Ë ™∫∞¢¶, ·Ó Î·È ·ÔÙÂÏ› Û¿ÓÈ· ·ÈÙ›· ·Ó·Ó¢ÛÙÈ΋˜ ‰˘Û¯¤ÚÂÈ·˜ ÛÙË ÓÂÔÁÓÈ΋ ËÏÈΛ·, ··ÈÙ› ¿ÌÂÛË ·Ó·ÁÓÒÚÈÛË, ηıÒ˜ ÛÙȘ ÂÚÈÛÛfiÙÂÚ˜ ÂÚÈÙÒÛÂȘ ¤¯ÂÈ Î·Ï‹ ÚfiÁÓˆÛË ÌÂÙ¿ ·fi ¤ÁηÈÚË ¯ÂÈÚÔ˘ÚÁÈ΋ ·ÓÙÈÌÂÙÒÈÛË. ∂›Û˘, ·fi Ù· Â˘Ú‹Ì·Ù· Ù˘ ÂÚ›ÙˆÛ˘ ™∫∞¢¶ Ù‡Ô˘ 4 ÚÔÛÙ›ıÂÓÙ·È ÂӉ›ÍÂȘ ÛÙ· ‹‰Ë ˘¿Ú¯ÔÓÙ·
‰Â‰Ô̤ӷ Û¯ÂÙÈο
1. Laberge JM, Flageole H, Pugash D, Khalife S, Blair G, Filiatrault D et al. Outcome of the prenatally diagnosed congenital cystic adenomatoid lung malformation: a
Canadian experience. Fetal Diagn Ther 2001;16:178-186.
2. Miller JA, Corteville JE, Langer JC. Congenital cystic adenomatoid malformation in the fetus: natural history and predictors of outcome. J Pediatr Surg 1996;31:805-808.
3. Thorpe-Beeston JG, Nicolaides KH. Cystic adenomatoid malformation of the lung: prenatal diagnosis and outcome. Prenat Diagn 1994;14:677-688.
4. Stocker JT, Madewell JE, Drake RM. Congenital cystic adenomatoid malformation of the lung. Classification and morphologic spectrum. Hum Pathol 1977;8:155-171.
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6. Morotti RA, Cangiarella J, Gutierrez MC, Jagirdar J, Askin F, Singh G et al. Congenital cystic adenomatoid malformation of the lung (CCAM): evaluation of the cellular components. Hum Pathol 1999;30:618-625.
7. van Koningsbruggen S, Ahrens F, Brockmann M, Michalk D, Rietschel E. Congenital cystic adenomatoid malformation type 4. Pediatr Pulmonol 2001;32:471-475.
8. Conran RM, Stocker JT. Extralobar sequestration with frequently associated congenital cystic adenomatoid malformation, type 2: report of 50 cases. Pediatr Dev Pathol 1999;2:454-463.
9. Winters WD, Effmann EL, Nghiem HV, Nyberg DA. Disappearing fetal lung masses: importance of postnatal imaging studies. Pediatr Radiol 1997;27:535-539.
10. Roggin KK, Breuer CK, Carr SR, Hansen K, Kurkchubasche AG, Wesselhoeft CW Jr et al. The unpredictable character of congenital cystic lung lesions. J Pediatr Surg 2000;35:801-805.
11. Bagolan P, Nahom A, Giorlandino C, Trucchi A, Bilancioni E, Inserra A et al. Cystic adenomatoid malformation of the lung: clinical evolution and management. Eur J Pediatr 1999;158:879-882.
12. Waszak P, Claris O, Lapillonne A, Picaud JC, Basson E, Chappuis JP et al. Cystic adenomatoid malformation of the lung: neonatal management of 21 cases. Pediatr Surg Int 1999;15:326-331.
13. Morotti RA, Gutierrez MC, Askin F, Profitt SA, Wert SE, Whitsett JA et al. Expression of thyroid transcription factor1 in congenital cystic adenomatoid malformation of the lung. Pediatr Dev Pathol 2000;3:455-461.
14. Mahle WT, Rychik J, Tian ZY, Cohen MS, Howell LJ, Crombleholme TM et al. Echocardiographic evaluation of the fetus with congenital cystic adenomatoid malformation. Ultrasound Obstet Gynecol 2000;16:620-624.
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19. Monni G, Paladini D, Ibba RM, Teodoro A, Zoppi MA, Lamberti A et al. Prenatal ultrasound diagnosis of congenital cystic adenomatoid malformation of the lung: a report of 26 cases and review of the literature. Ultrasound Obstet Gynecol 2000;16:159-162.
20. Dommergues M, Louis-Sylvestre C, Mandelbrot L, Aubry MC, Revillon Y, Jarreau PH et al. Congenital adenomatoid malformation of the lung: when is active fetal therapy indicated? Am J Obstet Gynecol 1997;177:953-958.
21. Neilson IR, Russo P, Laberge JM, Filiatrault D, Nguyen LT, Collin PP et al. Congenital adenomatoid malformation of the lung: current management and prognosis. J Pediatr Surg 1991;26:975-980.
22. Marshall KW, Blane CE, Teitelbaum DH, van Leeuwen K. Congenital cystic adenomatoid malformation: impact of prenatal diagnosis and changing strategies in the treatment of the asymptomatic patient. Am J Roentgenol 2000;175:1551-1554.
23. dell’Agnola C, Tadini B, Mosca F, Colnaghi M, Wesley J. Advantages of prenatal diagnosis and early surgery for congenital cystic disease of the lung. J Perinat Med 1996;24:621-631.
24. Shariff S, Thomas JA, Shetty N, D’Cunha S. Primary pulmonary rhabdomyosarcoma in a child, with a review of literature. J Surg Oncol 1988;38:261-264.
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HÌÂÚÔÌËÓ›· ˘Ô‚ÔÏ‹˜: 22-11-2002
HÌÂÚÔÌËÓ›· ¤ÁÎÚÈÛ˘: 17-02-2003
¢È‡ı˘ÓÛË ·ÏÏËÏÔÁÚ·Ê›·˜: µ·ÛÈÏÈ΋ ¢ÚfiÛÔ˘-∞Á·Î›‰Ô˘
°ÏËÓÔ‡ 28, ∆.∫. 543 52, £ÂÛÛ·ÏÔÓ›ÎË
E-mail: agaki@med.auth.gr
∂ÈÛ·ÁˆÁ‹: ∏ Îڤ̷ pimecrolimus 1% (Elidel, SDZ ASM 981) Â›Ó·È ÌË ÛÙÂÚÈÓÔÂȉ‹˜ ÂÎÏÂÎÙÈÎfi˜ ·Ó·ÛÙÔϤ·˜ ÙˆÓ ÊÏÂÁÌÔÓˆ-
‰ÒÓ Î˘ÙÙ·ÚÔÎÈÓÒÓ, Ô˘ ¯ÚËÛÈÌÔÔÈÂ›Ù·È ÙÔÈο ÛÙË ıÂڷ›·
Ù˘ ·ÙÔÈ΋˜ ‰ÂÚÌ·Ù›Ùȉ·˜. ∏ ·ÚÔ‡Û· ÌÂϤÙË ‰ÈÂÚÂ˘Ó¿ ÙËÓ Â›‰Ú·ÛË Ù˘ ÚÒÈÌ˘ ıÂڷ¢ÙÈ΋˜ ·Ú¤Ì‚·Û˘ Ì Îڤ̷ pimecrolimus ÛÙË Ì·ÎÚÔ¯ÚfiÓÈ· ¤Î‚·ÛË Ù˘ ÓfiÛÔ˘.
™ÎÔfi˜: ™ÎÔfi˜ Ù˘ ÌÂϤÙ˘ ‹Ù·Ó Ó· ·ÍÈÔÏÔÁ‹ÛÂÈ ·Ó Ë ÚÒÈ-
ÌË ıÂڷ¢ÙÈ΋ ·Ú¤Ì‚·ÛË Ì pimecrolimus Û ‚Ú¤ÊË ÌÂ
·ÙÔÈ΋ ‰ÂÚÌ·Ù›Ùȉ· ÌÔÚ› Ó· ÂËÚ¿ÛÂÈ ÙË Ì·ÎÚÔ¯ÚfiÓÈ·
ÔÚ›· Ù˘ ÓfiÛÔ˘, ÚÔÏ·Ì‚¿ÓÔÓÙ·˜ ÙȘ ÂÍ¿ÚÛÂȘ.
ÀÏÈÎfi Î·È Ì¤ıÔ‰ÔÈ: ¶Ú·ÁÌ·ÙÔÔÈ‹ıËΠ̛· ‰ÈÏ‹-Ù˘ÊÏ‹ ÌÂ-
ϤÙË, ‰È¿ÚÎÂÈ·˜ ÂÓfi˜ ¤ÙÔ˘˜, Û 251 ‚Ú¤ÊË ËÏÈΛ·˜ 3-23 ÌËÓÒÓ
Ô˘ Ù˘¯·ÈÔÔÈ‹ıËÎ·Ó Ì ÏfiÁÔ 4:1 Û ‰‡Ô ıÂڷ¢ÙÈΤ˜ ÔÌ¿‰Â˜: ÛÙËÓ ÚÒÙË ÂÊ·ÚÌfiÛÙËΠÛ··ÛÌ· pimecrolimus (n=204) Î·È ÛÙË ‰Â‡ÙÂÚË Û˘Ì‚·ÙÈ΋ ıÂڷ¢ÙÈ΋ ·ÁˆÁ‹ (n=47). ∫·È ÛÙȘ ‰‡Ô ÔÌ¿‰Â˜ ÂÈÙÚÂfiÙ·Ó Ë ¯Ú‹ÛË Ì·Ï·ÎÙÈ-
ÎÒÓ ÁÈ· ÙËÓ ÍËÚÔ‰ÂÚÌ›· Î·È ÙÔÈÎÒÓ ÎÔÚÙÈÎÔÛÙÂÚÔÂȉÒÓ ÁÈ· ÙËÓ ·ÓÙÈÌÂÙÒÈÛË ÙˆÓ ÂÍ¿ÚÛÂˆÓ Ù˘ ÓfiÛÔ˘. ™ÙËÓ ÂÚ›ÙˆÛË
ÚÒÈÌˆÓ ÛËÌ›ˆÓ Î·È Û˘ÌÙˆÌ¿ÙˆÓ ‰ÂÚÌ·Ù›Ùȉ·˜, ¯ÚËÛÈÌÔ-
ÔÈ‹ıËΠÎڤ̷ pimecrolimus ‹ ÌfiÓÔ ¤Î‰Ô¯Ô. ∏ ·ÔÙÂÏÂ-
ÛÌ·ÙÈÎfiÙËÙ· Ù˘ ÂÊ·ÚÌÔ˙fiÌÂÓ˘ ·ÁˆÁ‹˜ ÂÎÙÈÌ‹ıËΠ̠‚¿-
ÛË ÙËÓ Â›ÙˆÛË ÙˆÓ ÂÍ¿ÚÛÂˆÓ ÛÙÔ˘˜ 6 Ì‹Ó˜ ·fi ÙËÓ ¤Ó·Ú-
Ù˘ ıÂڷ›·˜.
ÔÏÔÎÏËÚÒÓÂÈ ÙÔ ÂÍ¿ÌËÓÔ Ù˘ ÌÂϤÙ˘ ¯ˆÚ›˜ η̛· ¤Í·ÚÛË, Û ۯ¤ÛË Ì 34,8% ÙˆÓ Ì·ÚÙ‡ÚˆÓ (p<0,001), ÂÓÒ 56,9% ¤Ó·ÓÙÈ 28,3%, ·ÓÙ›ÛÙÔȯ·, ¯ˆÚ›˜ ¤Í·ÚÛË Î·Ù¿ ÙË ‰È¿ÚÎÂÈ· ÂÓfi˜ ¤ÙÔ˘˜. ∂ÈϤÔÓ, Ë ¯Ú‹ÛË ÙˆÓ ÎÔÚÙÈÎÔÛÙÂÚÔÂȉÒÓ ÛÙËÓ ÔÌ¿‰· ÙÔ˘ pimecrolimus ‹Ù·Ó ·ÈÛıËÙ¿ ÂÚÈÔÚÈṲ̂ÓË: 63,7% ÙˆÓ ·ÛıÂÓÒÓ ‰ÂÓ ¯ÚËÛÈÌÔÔ›ËÛ ηıfiÏÔ˘ ÛÙÂÚÔÂȉ‹, Û ۯ¤ÛË Ì 34,8% ÙˆÓ Ì·ÚÙ‡ÚˆÓ. ∆Ô pimecrolimus ‹Ù·Ó ›Û˘ ÈÔ ·ÔÙÂÏÂÛÌ·ÙÈÎfi ÛÙÔÓ ¤ÏÂÁ¯Ô ÙÔ˘ ÎÓËÛÌÔ‡ Î·È ÙˆÓ ÛËÌ›ˆÓ Ù˘ ·ÙÔÈ΋˜ ‰ÂÚÌ·Ù›Ùȉ·˜. ¢ÂÓ ˘‹Ú¯·Ó ÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈΤ˜ ‰È·ÊÔÚ¤˜ fiÛÔÓ ·ÊÔÚ¿ ÛÙȘ ·ÓÂÈı‡ÌËÙ˜ ÂÓ¤ÚÁÂȘ. ™˘ÌÂÚ¿ÛÌ·Ù·: ∏ ıÂڷ›· ÙˆÓ ÚÒÈÌˆÓ ÛËÌ›ˆÓ Î·È Û˘ÌÙˆÌ¿ÙˆÓ ·ÙÔÈ΋˜ ‰ÂÚÌ·Ù›Ùȉ·˜ Ì pimecrolimus ÌÔÚ› Ó· ·ÏÏ¿ÍÂÈ ÛËÌ·ÓÙÈο ÙËÓ ÔÚ›· Ù˘ ÓfiÛÔ˘, ÌÂÈÒÓÔÓÙ·˜ ÙȘ ÂÍ¿ÚÛÂȘ Î·È ‚ÂÏÙÈÒÓÔÓÙ·˜ ÙÔÓ ÁÂÓÈÎfi ¤ÏÂÁ¯Ô Ù˘ ÓfiÛÔ˘. ∆Ô pimecrolimus ‹Ù·Ó ·ÛʷϤ˜ Î·È Î·Ï¿ ·ÓÂÎÙfi.
1Kapp A, Papp K, Bingham A, Folster-Holst R, Ortonne JP, Potter PC et al Long-term management of atopic dermatitis in infants with topical pimecrolimus, a nonsteroid antiinflammatory drug J Allergy Clin Immunol 2002;110:277-284 ∂ϤÓË µÔÏÔÓ¿ÎË
∂¶π∫∞πƒ∞ £∂ª∞∆∞CURRENT
ISSUES
§Â˘ÎÔÙÚȤÓÈ·
Î·È ÊÏÂÁÌÔÓ‹: ÓÂfiÙÂÚË Ê·ÚÌ·ÎÔÏÔÁÈ΋ ıÂÒÚËÛË
∞. ∆˘ÏÈÁ¿‰·, °. ∞ÓÙˆÓÔÁÂÒÚÁÔ˜
Leukotrienes and inflammation: current pharmacological perspective ∂. Tiligada, G. Antonogeorgos
¶ÂÚ›ÏË„Ë: ∆· Ï¢ÎÔÙÚȤÓÈ· (L∆s) Â›Ó·È ÂÓ‰ÔÁÂÓ›˜ ÏÈȉÈÎÔ› ÌÂÛÔÏ·‚ËÙ¤˜ Ô˘ Û˘ÓÙ›ıÂÓÙ·È de novo Ì ‰È·Î˘ÙÙ¿ÚÈÔ ÌÂÙ·‚ÔÏÈÛÌfi, ̤ۈ Ù˘ Ô‰Ô‡ Ù˘ 5-ÏÈÔ͢ÁÂÓ¿Û˘. ™˘ÌÌÂÙ¤¯Ô˘Ó ÛÙËÓ ·ıÔÁ¤ÓÂÈ· ÙÔ˘ ¿ÛıÌ·ÙÔ˜ Î·È ¿ÏÏˆÓ ÊÏÂÁÌÔÓˆ‰ÒÓ ‰È·‰ÈηÛÈÒÓ Î·È ÛÙËÓ ¿Ì˘Ó· ÙÔ˘ ÍÂÓÈÛÙ‹. OÌ·‰ÔÔÈÔ‡ÓÙ·È Û ΢ÛÙÂ˚Ó˘ÏÈο ·Ó¿ÏÔÁ· (cys-LTs) Î·È ÛÙÔ LTB4 Î·È ·ÛÎÔ‡Ó ÙË ‰Ú¿ÛË ÙÔ˘˜ ̤ۈ ‰È·ÎÚÈÙÒÓ ˘ÔÙ‡ˆÓ ˘Ô‰Ô¯¤ˆÓ. ™ÙËÓ ·ÚÔ‡Û· ·Ó·ÛÎfiË-
ÛË ·ÚÔ˘ÛÈ¿˙ÔÓÙ·È Ù· Ê·ÚÌ·ÎÔÏÔÁÈο ¯·Ú·ÎÙËÚÈ-
ÛÙÈο Ù˘ Û‡ÓıÂÛ˘, ÙÔ˘ ÌÂÙ·‚ÔÏÈÛÌÔ‡ Î·È Ù˘
‰Ú¿Û˘ ÙˆÓ L∆s, ÔÈ È‰ÈfiÙËÙ˜ ÙˆÓ ˘Ô‰Ô¯¤ˆÓ ÙÔ˘˜ Î·È Ë ÎÏÈÓÈ΋ ÂÊ·ÚÌÔÁ‹ ÙˆÓ ÙÚÔÔÔÈËÙÒÓ ÙˆÓ
Ï¢ÎÔÙÚÈÂÓ›ˆÓ.
§¤ÍÂȘ ÎÏÂȉȿ: Ï¢ÎÔÙÚȤÓÈ·, ˘Ô‰Ô¯Â›˜, ÙÚÔÔÔÈËÙ¤˜.
™˘ÓÙÔÌÔÁڷʛ˜
AIAÕÛıÌ· ÌÂÙ¿ ·fi ¯ÔÚ‹ÁËÛË ·ÛÈÚ›Ó˘
BLTÀÔ‰Ô¯¤·˜ ÙÔ˘ Ï¢ÎÔÙÚÈÂÓ›Ô˘ µ4
cPLA2 ∫˘ÙÔÛÔÏÈ΋ ʈÛÊÔÏÈ¿ÛË ∞2 cysLT(s)∫˘ÛÙÂ˚Ó˘ÏÈÎfi(¿) Ï¢ÎÔÙÚȤÓÈÔ(·) FLAP¶ÚˆÙ½ÓË ÂÓÂÚÁÔÔ›ËÛ˘ Ù˘ 5-ÏÈÔ͢ÁÂÓ¿Û˘
GPCRÀÔ‰Ô¯¤·˜ Û˘Ó‰ÂfiÌÂÓÔ˜ Ì ڈÙ½Ó˜ G 5-HpETE5-˘‰ÚÔÂÚÔ͢-ÂÈÎÔÛ·ÙÂÙÚ·ÓÔ˚Îfi Ô͇
ILπÓÙÂÚÏ¢ΛÓË
5-LO5-ÏÈÔ͢ÁÂÓ¿ÛË LT(s)§Â˘ÎÔÙÚȤÓÈÔ(·)
MAP¶ÚˆÙ½ÓË ÂÓÂÚÁÔÔÈÔ‡ÌÂÓË ·fi ÌÈÙÔÁfiÓ·
MAPK∫ÈÓ¿ÛË Ù˘ ª∞ƒ ORF¶Ï·›ÛÈÔ ·Ó¿ÁÓˆÛ˘ PAF¶·Ú¿ÁÔÓÙ·˜ ÂÓÂÚÁÔÔ›ËÛ˘ ÙˆÓ ·ÈÌÔÂÙ·Ï›ˆÓ
PGE2 ¶ÚÔÛÙ·ÁÏ·Ó‰›ÓË ∂2
ROS∂ÓÂÚÁ¿ ·Ú¿ÁˆÁ· Ô͢ÁfiÓÔ˘
SRSµÚ·‰¤ˆ˜-·ÓÙȉÚÒÛ· Ô˘Û›·
∂ÚÁ·ÛÙ‹ÚÈÔ º·ÚÌ·ÎÔÏÔÁ›·˜, π·ÙÚÈ΋ ™¯ÔÏ‹ ¶·ÓÂÈÛÙËÌ›Ô˘ ∞ıËÓÒÓ
Abstract: Leukotrienes (L∆s) are endogenous lipid mediators, which are synthesised de novo via intercellular metabolic processes, through the 5lipoxygenase pathway. ∆hey are involved in the pathogenesis of asthma and other inflammatory processes and in the host defence response. They are sub-grouped into cysteinyl-LTs (cys-LTs) and LTB4 and exert their action via distinct receptors. This review presents the pharmacological characteristics of the synthesis, metabolism and action of LTs, the properties of their receptors and the clinical application of the leukotriene modifiers.
Key words: leukotrienes, receptors, modifiers.
SRS-AµÚ·‰¤ˆ˜-·ÓÙȉÚÒÛ· Ô˘Û›· Ù˘ ·Ó·Ê˘Ï·Í›·˜ 7TM∂Ù¿ ‰È·ÌÂÌ‚Ú·ÓÈΤ˜ ÂÚÈÔ¯¤˜ TNFOÁÎÔÓÂÎÚˆÙÈÎfi˜ ·Ú¿ÁÔÓÙ·˜
∂ÈÛ·ÁˆÁ‹ ¶ÚÈÓ 60 ¯ÚfiÓÈ·, ‹Ù·Ó ÁÓˆÛÙfi fiÙÈ Ì›· ‚Ú·‰¤ˆ˜·ÓÙȉÚÒÛ· Ô˘Û›· (SRS, slow-reacting substance), ÂÎÏ˘fiÌÂÓË ·fi ÙÔ˘˜ Ó‡ÌÔÓ˜ ÌÂÙ¿ ·fi ·ÓÙÈÁÔÓÈ΋ ‰È¤ÁÂÚÛË, ›¯Â ÙËÓ ÈηÓfiÙËÙ· Ó· Û˘Û¿ ÙÔ˘˜ Ï›Ԣ˜ Ì˘˜ (1). ∂›ÎÔÛÈ ¯ÚfiÓÈ· ·ÚÁfiÙÂÚ·, ÌÂÙÔÓÔÌ¿ÛÙËΠ۠‚Ú·‰¤ˆ˜-·ÓÙȉÚÒÛ· Ô˘Û›· Ù˘ ·Ó·Ê˘Ï·Í›·˜ (SRS-A, slow-reacting substance of anaphylaxis), ÂÂȉ‹ Ë ·Ú·ÁˆÁ‹ Ù˘ Û¯ÂÙÈ˙fiÙ·Ó Ì ÙËÓ ·ÂÏ¢ı¤ÚˆÛË ÈÛÙ·Ì›Ó˘ ηٿ ÙÔ ·Ó·Ê˘Ï·ÎÙÈÎfi ÛÔÎ (2). ∆Ô 1979, Ë SRS-A Ù·˘ÙÔÔÈ‹ıËÎÂ Î·È ÔÓÔÌ¿ÛÙËΠϢÎÔÙÚȤÓÈÔ (LT), ‰Â‰Ô̤ÓÔ˘ fiÙÈ ÙÔ ÌfiÚÈÔ ‹Ù·Ó ‰ÔÌÈο Û˘ÁÁÂÓ¤˜ Ì ٷ ÌÂÙ·‚ÔÏÈο ÚÔ˚fiÓÙ· ÙÔ˘ ·Ú·¯È‰ÔÓÈÎÔ‡ Ôͤˆ˜ ÛÙ· Ï¢ÎÔ·ÙÙ·Ú· ηÈ
Laboratory of Pharmacology, Medical School of University of Athens
(LT). ∆Ô ·Ú·¯È‰ÔÓÈÎfi Ô͇ (∞∞) ·ÂÏ¢-
ıÂÚÒÓÂÙ·È ·fi Ù· ÌÂÌ‚·ÓÈο ʈÛÊÔÏÈ›‰È· (PL) ̤ۈ Ù˘ ʈÛÊÔÏÈ¿Û˘ ∞2 (cPLA2) Î·È ÌÂÙ·ÙÚ¤ÂÙ·È Û LT∞4 ·fi ÙËÓ 5-ÏÈÔ͢ÁÂÓ¿ÛË (5-LO) ̤ۈ Ù˘ ÚˆÙ½Ó˘ ÂÓÂÚÁÔÔ›ËÛ˘ Ù˘ 5-ÏÈÔ͢ÁÂÓ¿Û˘ (FLAP). ™Ù· ˈÛÈÓfiÊÈÏ·, ‚·ÛÂfiÊÈÏ· Î·È ÛÈÙ¢ÙÈο ·ÙÙ·Ú·, ÙÔ LT∞4 ÌÂÙ·ÙÚ¤ÂÙ·È Û LTC4 ( ), ÙÔ ÔÔ›Ô ÌÂٷʤÚÂÙ·È ÛÙÔÓ ÂÍˆÎ˘ÙÙ¿ÚÈÔ ¯ÒÚÔ, fiÔ˘ ‰È·Û¿Ù·È Û LTD4 Î·È LT∂4. ™Ù· ÌÔÓÔ·ÙÙ·Ú·, Ù· Ì·ÎÚÔÊ¿Á· Î·È Ù· Ô˘‰ÂÙÂÚfiÊÈÏ·, ÙÔ LT∞4 ÌÂÙ·ÙÚ¤ÂÙ·È Û LTB4 ( ). ∆· ÂÚ˘ıÚÔ·ÙÙ·Ú· Î·È Ù·
∆-ÏÂÌÊÔ·ÙÙ·Ú· Û˘Óı¤ÙÔ˘Ó LTB4, ÂÓÒ Ù· ÂÓ‰ÔıËÏȷο ·ÙÙ·Ú· Î·È Ù· ·ÈÌÔÂÙ¿ÏÈ· (∞) Û˘Óı¤ÙÔ˘Ó LTC4 Î·È LTB4 ·fi ÙÔ LT∞4
Ô˘ ·ÂÏ¢ıÂÚÒÓÂÙ·È ·fi Ù· ·Ú·Î›ÌÂÓ· Ô˘‰ÂÙÂÚfiÊÈÏ· ( ). (BLT: ˘Ô‰Ô¯¤·˜ LTB4, cysLT1: ˘Ô‰Ô¯¤·˜ ΢ÛÙÂ˚ÓÈÏÈÎÒÓ L∆s 1, Glu: ÁÏÔ˘Ù·ÌÈÎfi Ô͇, Gly: ÁÏ˘Î›ÓË, GSH: ÁÏÔ˘Ù·ıÂÈfiÓË, IgE: ·ÓÔÛÔÛÊ·ÈÚ›ÓË ∂, ∆: ÌÂÙ·ÊÔÚ¤·˜ LTC4, TH2: ‚ÔËıËÙÈο ∆-ÏÂÌÊÔ·ÙÙ·Ú· 2).
ÙËÓ ÂÈıËÏȷ΋ ¤ÎÎÚÈÛË, ÂÓÒ Ë ¤ÎÊÚ·ÛË ÙˆÓ ˘Ô‰Ô¯¤ˆÓ ÙÔ˘˜ ÛÙÔÓ Ó‡ÌÔÓ· ¤¯ÂÈ È‰È·›ÙÂÚË ÛËÌ·Û›· ÏfiÁˆ Ù˘ Û˘ÌÌÂÙÔ¯‹˜ ÙÔ˘˜ ÛÙËÓ ·ıÔÊ˘ÛÈÔÏÔÁ›· ÙÔ˘ ¿ÛıÌ·ÙÔ˜. ™ÙȘ ÂÚÈÛÛfiÙÂÚ˜ ·Ó·ÊÔÚ¤˜, Ë Î·ÙËÁÔÚÈÔÔ›ËÛË ÙˆÓ ˘Ô‰Ô¯¤ˆÓ ÙˆÓ cysLTs ‚·Û›˙ÂÙ·È ÛÙȘ Ê·ÚÌ·ÎÔÏÔÁÈΤ˜ ȉÈfiÙËÙ˜ ÙˆÓ ·ÓÙ·ÁˆÓÈÛÙÒÓ, ÂÓÒ ‰ÂÓ ·ÔÎÏ›ÂÙ·È ÂÚ·ÈÙ¤Úˆ ÂÙÂÚÔÁ¤ÓÂÈ·, Ë ÔÔ›· ·ÔÚÚ¤ÂÈ ·fi ÙË ‰È·ÊÔÚÂÙÈ΋ ÈÛ¯‡ Î·È Û˘ÁÁ¤ÓÂÈ· ÙˆÓ ÂÓ‰ÔÁÂÓÒÓ ÚÔÛ‰ÂÌ¿ÙˆÓ, ‰ËÏ·‰‹ ÙˆÓ ›‰ÈˆÓ ÙˆÓ LTs, ·ÏÏ¿ Î·È ·fi ÙËÓ Î·Ù·ÓÔÌ‹ ÙÔ˘˜ ÛÙÔ˘˜ ‰È¿ÊÔÚÔ˘˜ ÈÛÙÔ‡˜ ‰È·ÊfiÚˆÓ ÂȉÒÓ (25). ª¤¯ÚÈ Û‹ÌÂÚ· ¤¯Ô˘Ó ¯·Ú·ÎÙËÚÈÛÙ› ‰‡Ô ηÙËÁÔڛ˜ ˘Ô‰Ô¯¤ˆÓ ÙˆÓ cysLTs, Ô˘ ·Ó‹ÎÔ˘Ó ÛÙÔ˘˜ “˘Ô‰Ô¯Â›˜ Ô˘ Û˘Ó‰¤ÔÓÙ·È Ì ڈÙ½Ó˜ G (GPCR) Î·È Ê¤ÚÔ˘Ó ÂÙ¿ ‰È·ÌÂÌ‚Ú·ÓÈΤ˜ ÂÚÈÔ¯¤˜ (7TM)”. ∞˘ÙÔ› Â›Ó·È ÔÈ cysLT1 Î·È cysLT2 (¶›Ó·Î·˜ 1), ÂÓÒ Ì ‚¿ÛË ÙË ÌË ·ÓÙ·fiÎÚÈÛË Û ÁÓˆÛÙÔ‡˜
·ÓÙ·ÁˆÓÈÛÙ¤˜ ¤¯ÂÈ ÚÔÙ·ı› Î·È Ì›· ÙÚ›ÙË, ÔÈ cysLT3, ÔÈ ÔÔ›ÔÈ ÂÓÙÔ›˙ÔÓÙ·È ÛÙÔ ·Ú¤Á¯˘Ì· Ó¢ÌfiÓˆÓ ·ÓıÚÒˆÓ Î·È ÈÓ‰ÈÎÒÓ ¯ÔÈÚȉ›ˆÓ (26). Àԉԯ›˜ ÙÔ˘ LTB4 ∆Ô LTB4 ·›˙ÂÈ ÛËÌ·ÓÙÈÎfi ÚfiÏÔ ÛÙËÓ ¿Ì˘Ó· ÙÔ˘ ÍÂÓÈÛÙ‹, ‰ÈÂÁ›ÚÔÓÙ·˜ ÙËÓ ·ÂÏ¢ı¤ÚˆÛË Ï˘ÔÛˆ-
ÌÈ·ÎÒÓ ÂÓ˙‡ÌˆÓ Î·È ÂÓÂÚÁÒÓ ·Ú·ÁÒÁˆÓ Ô͢ÁfiÓÔ˘ (ROS, reactive oxygen species) ·fi Ù· ÎÔÎÎÈÔ·ÙÙ·Ú· Î·È Ù· Ì·ÎÚÔÊ¿Á· (16,23,27). ¶ÚfiÎÂÈÙ·È
ÁÈ· ÙÔ Î‡ÚÈÔ ÚÔ˚fiÓ ÙˆÓ Ô˘‰ÂÙÂÚfiÊÈÏˆÓ Î·È Ì·ÎÚÔÊ¿ÁˆÓ Î·È ‰È·ı¤ÙÂÈ ÙËÓ ÈηÓfiÙËÙ· ·Ó¿ÎÙËÛ˘ ηÈ
ÂÓÂÚÁÔÔ›ËÛ˘ ¢ڤˆ˜ Ê¿ÛÌ·ÙÔ˜ ·ÓÔÛÔÏÔÁÈÎÒÓ ÌÂÛÔÏ·‚ËÙÒÓ (20). ¶ÂÚÈÁÚ¿ÊÂÙ·È ˆ˜ ÈÛ¯˘Úfi˜ ¯ËÌÂÈÔÙ·ÎÙÈÎfi˜ ·Ú¿ÁÔÓÙ·˜, Ô ÔÔ›Ô˜ Û˘ÌÌÂÙ¤¯ÂÈ ÛÙËÓ ¤Ó·ÚÍË, ÙÔ Û˘ÓÙÔÓÈÛÌfi Î·È ÙËÓ ÂÓ›Û¯˘ÛË Ù˘ ÊÏÂÁÌÔÓÒ‰Ô˘˜ ·¿ÓÙËÛ˘, ηÙ¢ı‡ÓÔÓÙ·˜ ÙËÓ Î›-
¶›Ó·Î·˜ 1. ÷ڷÎÙËÚÈÛÙÈο ÙˆÓ ˘Ô‰Ô¯¤ˆÓ ÙˆÓ
(25,65-67)
CysLT1 CysLT2
™˘ÁÁ¤ÓÂÈ·: LTD4 > LTC4 > LTE4
™˘ÁÁ¤ÓÂÈ·: LTC4 = LTD4>> LTE4
∞ÓÙ·ÁˆÓÈÛÙ¤˜
BAYu9773 (ÌË ÂÎÏÂÎÙÈÎfi˜), MK571BAYu9773 (ÌË ÂÎÏÂÎÙÈÎfi˜)
CGP45715∞ (ÈÚ·ÏÔ˘Î¿ÛÙË), LY170680
ICI204219 (˙·ÊÈÚÏÔ˘Î¿ÛÙË)
MK476 (ÌÔÓÙÂÏÔ˘Î¿ÛÙË)
ONO1078 (Ú·ÓÏÔ˘Î¿ÛÙË)
Ro24-5913 (ÛÈÓ·ÏÔ˘Î¿ÛÙË), ZK3523
SKF104353 (ÔÌÈÏÔ˘Î¿ÛÙË)
∫·Ù·ÓÔÌ‹ ÛÙÔÓ ¿ÓıÚˆÔ
§Â›Â˜ Ì˘˚Τ˜ ›Ó˜ ·ÂÚ·ÁˆÁÒÓ, Ì·ÎÚÔÊ¿Á· Ó‡ÌÔÓ·,∞ÓıÚÒÈÓ· ÂÚÈÊÂÚÈο Ï¢ÎÔ·ÙÙ·Ú·,
ÂÚÈÊÂÚÈο ÌÔÓÔ·ÙÙ·Ú·, ˈÛÈÓfiÊÈÏ·, ÛÏ‹Ó·˜ËˆÛÈÓfiÊÈÏ·, Ó¢ÌÔÓÈ΋ ÊϤ‚·, ÛÏ‹Ó·˜, ηډȿ, ÂÈÓÂÊÚ›‰È·, ∫¡™
ªÔÚȷο ¯·Ú·ÎÙËÚÈÛÙÈο
°ÔÓ›‰ÈÔ: Ãq13-q21°ÔÓ›‰ÈÔ: 13q14
¶ÚˆÙ½ÓË ·ÔÙÂÏÔ‡ÌÂÓË ·fi 338 ·ÌÈÓÔͤ·¶ÚˆÙ½ÓË ·ÔÙÂÏÔ‡ÌÂÓË ·fi 347 ·ÌÈÓÔͤ· 28% ÔÌÔÏÔÁ›· Ì ÙÔÓ BLT1 38% ÔÌÔÏÔÁ›· Ì ÙÔÓ cysLT1
ªÂÙ·‚›‚·ÛË ÙÔ˘ Û‹Ì·ÙÔ˜ ̤ۈ Gq/11, ·‡ÍËÛ˘ [Ca2+]i Î·È ÚˆÙÂ˚ÓÈ΋˜ ÎÈÓ¿Û˘ C
BLT1: ˘Ô‰Ô¯¤·˜ ÙÔ˘ Ï¢ÎÔÙÚÈÂÓ›Ô˘ LTB4, [Ca2+]i: ÂÓ‰Ô΢ÙÙ¿ÚÈ· Û˘ÁΤÓÙÚˆÛË ·Û‚ÂÛÙ›Ô˘ cysLT1: ˘Ô‰Ô¯¤·˜ ÙˆÓ Î˘ÛÙÂÓ˘ÏÈÎÒÓ Ï¢ÎÔÙÚÈÂÓ›ˆÓ-1
G: ÚˆÙ½ÓË G ∫¡™: ÎÂÓÙÚÈÎfi Ó¢ÚÈÎfi Û‡ÛÙËÌ·
2), ÙÔÓ ˘„ËÏ‹˜ Û˘ÁÁ¤ÓÂÈ·˜ µLT1 (12) ηÈÙÔÓ¯·ÌËÏ‹˜ Û˘ÁÁ¤ÓÂÈ·˜ µLT2 (28). OÈ ‰‡Ô ˘ÔÙ‡ÔÈ ·Ó‹-
ÎÔ˘Ó ÛÙÔ˘˜ “˘Ô‰Ô¯Â›˜ Ô˘ Û˘Ó‰¤ÔÓÙ·È Ì ڈ-
Ù½Ó˜ G (GPCR) Î·È Ê¤ÚÔ˘Ó ÂÙ¿ ‰È·ÌÂÌ‚Ú·ÓÈΤ˜
ÂÚÈÔ¯¤˜ (7TM)”, ·ÏÏ¿ ‰È·ı¤ÙÔ˘Ó ÌÈÎÚ‹ ÔÌÔÏÔÁ›·
Ì ¿ÏÏÔ˘˜ GPCR. ∆· ÁÔÓ›‰È¿ ÙÔ˘˜ Û¯ËÌ·Ù›˙Ô˘Ó Û˘-
ÛÙ¿‰· (gene cluster) ÛÙÔ ÁÔÓȉ›ˆÌ· ÙÔ˘ ·ÓıÚÒÔ˘ Î·È ÙÔ˘ ÔÓÙÈÎÔ‡, Ì ÛÙÂÓ¿ ·ÏÏËÏÔÂËÚ·˙fiÌÂÓË ¤ÎÊÚ·ÛË (29,30). ∂›Ó·È ÂӉȷʤÚÔÓ fiÙÈ Ô ˘ÔÎÈÓËÙ‹˜ ÙÔ˘ BLT1 ÂÓÙÔ›˙ÂÙ·È ÛÙÔ Ï·›ÛÈÔ ·Ó¿ÁÓˆÛ˘
(ORF) ÙÔ˘ BLT2. ™‹ÌÂÚ·, ‰ÈÂÚÂ˘Ó¿Ù·È Ë ·ÈÙ›· Ô˘
Ô‰‹ÁËÛ ÛÙÔ Û¯ËÌ·ÙÈÛÌfi Û˘ÛÙ¿‰ˆÓ ÁÔÓȉ›ˆÓ Ô˘
Έ‰ÈÎÔÔÈÔ‡Ó ˘Ô‰Ô¯Â›˜ Ï¢ÎÔÙÚÈÂÓ›ˆÓ, ·ÏÏ¿ ηÈ
¿ÏÏˆÓ ¯ËÌÂÈÔÂÏÎÙÈÎÒÓ ·Ú·ÁfiÓÙˆÓ Î·Ù¿ ÙË ‰È·‰È-
ηۛ· Ù˘ ÂͤÏÈ͢, ηıÒ˜ Î·È Ë ÁÂÓˆÌÈ΋ ÔÚÁ¿ÓˆÛË Ù˘ ÁÔÓȉȷ΋˜ ı¤Û˘ ÙˆÓ ˘Ô‰Ô¯¤ˆÓ ÙÔ˘ LTB4 ÛÙÔ ·ÓıÚÒÈÓÔ ¯ÚˆÌfiۈ̷ 14 (19,31,32).
Œ¯ÂÈ, ›Û˘, ÂÚÈÁÚ·Ê› Ô ˘ÚËÓÈÎfi˜ ˘Ô‰Ô¯¤·˜ PPAR· (peroxisome proliferator-activated receptor), ÛÙÔÓ ÔÔ›Ô ÚÔÛ‰¤ÓÂÙ·È ÙÔ LTB4 Î·È ÂÓÂÚÁÔÔÈ› ÙË ÌÂÙ·ÁÚ·Ê‹ ÁÔÓȉ›ˆÓ Ô˘ Û˘ÌÌÂÙ¤¯Ô˘Ó ÛÙË ÊÏÂÁÌÔÓÒ‰Ë ‰È·‰Èηۛ· (33).
º·ÚÌ·ÎÔÏÔÁÈΤ˜ ‰Ú¿ÛÂȘ
∆· ÌÂÙ·‚ÔÏÈο ÚÔ˚fiÓÙ· ÙÔ˘ ·Ú·¯È‰ÔÓÈÎÔ‡ Ôͤˆ˜, ÚÔÛÙ·ÁÏ·Ó‰›Ó˜ Î·È Ï¢ÎÔÙÚȤÓÈ·, Â›Ó·È ÛËÌ·ÓÙÈÎÔ› ÌÂÛÔÏ·‚ËÙ¤˜ Ù˘ ÊÏÂÁÌÔÓ‹˜, Ì ڈٷÁˆÓÈÛÙÈÎfi
ηٿ ÙËÓ ÂÈÛ‚ÔÏ‹ Í¤ÓˆÓ ÚÔ˜ ÙÔÓ ÔÚÁ·ÓÈÛÌfi Ô˘ÛÈÒÓ (8,25). ∏ ηٷÓÔÌ‹ ÙˆÓ ·Ó·‚ÔÏÈÎÒÓ ÂÓ˙‡ÌˆÓ Û ‰È¿ÊÔÚ· ·ÙÙ·Ú· ηıÈÛÙ¿ ÙË ‰È·Î˘ÙÙ¿ÚÈ· ÌÂÙ·ÊÔÚ¿ ÙÔ˘˜ Ô˘ÛÈ·ÛÙÈ΋ Û fi,ÙÈ ·ÊÔÚ¿ ÛÙË ‚ÈÔÛ‡ÓıÂÛË Î·È ÂÈÎÔÈÓˆÓ›· ÙˆÓ Ï¢ÎÔÙÚÈÂÓ›ˆÓ (6,21,22).
∆· cysLTs, LTC4 Î·È LTD4 Â›Ó·È ‚ÚÔÁ¯ÔÛ˘Û·ÛÙÈÎÔ› ·Ú¿ÁÔÓÙ˜, ÈÛ¯˘ÚfiÙÂÚÔÈ Ù˘ ÈÛÙ·Ì›Ó˘. ∆Ô LTE4, ·Ó Î·È ÏÈÁfiÙÂÚÔ ÈÛ¯˘Úfi, ÂÓÔ¯ÔÔÈÂ›Ù·È Î·È ·˘Ùfi, fiˆ˜ Î·È Ù· ˘fiÏÔÈ· cysLTs, ÁÈ· ÙËÓ ˘ÂÚ·ÓÙȉڷÛÙÈÎfiÙËÙ·, ÙËÓ ¤ÎÎÚÈÛË ‚ϤÓÓ˘ Î·È ÙËÓ ·fiÊÚ·ÍË ÙˆÓ ·ÂÚ·ÁˆÁÒÓ Û ·ÛıÌ·ÙÈÎÔ‡˜ ·ÛıÂÓ›˜ (8). ¶·Ú¿ÏÏËÏ·, Ù· cysLTs ÚÔ¿ÁÔ˘Ó ÙË ÌÂÙ·Ó¿ÛÙ¢ÛË ËˆÛÈÓÔÊ›ÏˆÓ ÛÙÔ˘˜ ·ÂÚ·ÁˆÁÔ‡˜ ·ÛıÌ·ÙÈÎÒÓ ·ÛıÂÓÒÓ. ∆· ·ÙÙ·Ú· Ô˘ Û˘ÌÌÂÙ¤¯Ô˘Ó ÛÙȘ ·ÓÙȉڿÛÂȘ ˘ÂÚ¢·ÈÛıËÛ›·˜ Ù‡Ô˘ π ‰È·ı¤ÙÔ˘Ó Ì˯·ÓÈÛÌfi Û‡ÓıÂÛ˘ Î·È ·ÂÏ¢ı¤ÚˆÛ˘ ÙˆÓ cysLTs. ™ÙÔ˘˜ ÊÏÂÁÌ·›ÓÔÓÙ˜ ·ÛıÌ·ÙÈÎÔ‡˜ ·ÂÚ·ÁˆÁÔ‡˜, Û ·ÓÙ›ıÂÛË Ì ÙÔÓ ÂÍ·ÎÚÈ‚ˆÌ¤ÓÔ ÚfiÏÔ ÙˆÓ ËˆÛÈÓÔÊ›ÏˆÓ Ó· ·ÂÏ¢ıÂÚÒÓÔ˘Ó ÙÔÍÈΤ˜ ‚·ÛÈΤ˜ ÚˆÙ½Ó˜ Î·È LTC4 (14), Ô ÚfiÏÔ˜ ÙˆÓ Ô˘‰ÂÙÂÚÔÊ›ÏˆÓ ‰ÂÓ Â›Ó·È Î·Ù·ÓÔËÙfi˜, ·Ú’ fiÏÔ Ô˘ ·ÓȯÓ‡ÔÓÙ·È ÛÙÔ˘˜ ·ÂÚ·ÁˆÁÔ‡˜ ·ÛıÂÓÒÓ Ì ¯ÚfiÓÈÔ ÛÔ‚·Úfi ¿ÛıÌ· (27). ∆Ô LTB4 ÂËÚ¿˙ÂÈ ÙËÓ ÂÈÛÚÔ‹ Ô˘‰ÂÙÂÚÔÊ›ÏˆÓ ÌÂÙ¿ ·fi ÚfiÎÏËÛË Ì ·ÓÙÈÁfiÓ·, ·ÏÏ¿ Ë ÏÂÈÙÔ˘ÚÁÈ΋ ÛËÌ·Û›· ÙÔ˘ Ê·ÈÓÔ̤ÓÔ˘ ÛÙÔ ¿ÛıÌ· ·ÌÊÈÛ‚ËÙÂ›Ù·È (34). ¶Ú¤ÂÈ, ¿ÓÙˆ˜, Ó· ÛËÌÂȈı› fiÙÈ Ù· ÁÔÓ›‰È· Ô˘ Έ‰ÈÎÔÔÈÔ‡Ó ÙÔ˘˜ ˘Ô‰Ô¯Â›˜ ÙÔ˘ LTB4 ÂÓÙÔ›˙ÔÓÙ·È ÏËÛ›ÔÓ Ì›·˜ ·fi ÙȘ ÂÚÈÔ¯¤˜ ÙÔ˘ ÁÔÓȉÈÒÌ·ÙÔ˜ Ô˘ ¤¯Ô˘Ó
¶›Ó·Î·˜ 2. ÷ڷÎÙËÚÈÛÙÈο ÙˆÓ ˘Ô‰Ô¯¤ˆÓ ÙÔ˘ LTB4 (12,19,28,30,32,68,69)
µLT1 µLT2
∞ÓÙ·ÁˆÓÈÛÙ¤˜
CP105696, U75302, CP195543, O¡O4057LY255283, ZK158252, O¡O4057
∫˘Ú›ˆ˜ ÂÚÈÊÂÚÈο Ï¢ÎÔ·ÙÙ·Ú· ηÈ
∫·Ù·ÓÔÌ‹
∂˘Ú›· ¤ÎÊÚ·ÛË Î˘Ú›ˆ˜ ÛÙÔ ÛÏ‹Ó·
ÂÚÈÙÔÓ·˚ο Ì·ÎÚÔÊ¿Á·, ¯·ÌËÏ‹ ¤ÎÊÚ·ÛË◊·Ú, ˆÔı‹ÎË, Ï¢ÎÔ·ÙÙ·Ú·, ηډȿ, ÓÂÊÚÔ›, ÛÙÔ ı‡ÌÔ Î·È ÛÏ‹Ó·Ï·ÎÔ‡ÓÙ·˜, ÂÁΤʷÏÔ˜
ªÔÚȷο ¯·Ú·ÎÙËÚÈÛÙÈο
°ÔÓ›‰ÈÔ: 14q11.2-q12°ÔÓ›‰ÈÔ ·ÓÔ‰Èο ÙÔ˘ BLT1
¶ÚˆÙ½ÓË ·ÔÙÂÏÔ‡ÌÂÓË ·fi 352 ·ÌÈÓÔͤ·¶ÚˆÙ½ÓË ·ÔÙÂÏÔ‡ÌÂÓË ·fi 358 ·ÌÈÓÔͤ· ∂ÓÂÚÁÔÔ›ËÛË Gi Î·È G16, ·Ó·ÛÙÔÏ‹ ·‰ÂÓ˘ÏÔ΢ÎÏ¿Û˘,∂ÓÂÚÁÔÔ›ËÛË Gi, Gz, Gq, ·‡ÍËÛË πƒ3, ·Ó·ÛÙÔÏ‹
ÂÓÂÚÁÔÔ›ËÛË ÊˆÛÊÔÏÈ¿Û˘ C, ÎÈÓËÙÔÔ›ËÛË Ca2+i ·‰ÂÓ˘ÏÔ΢ÎÏ¿Û˘
28% ÔÌÔÏÔÁ›· ÌÂ ÙÔÓ cysLT1
39-45% ÔÌÔÏÔÁ›· Ì ÙÔÓ BLT1 ƒ‡ıÌÈÛË ÌÂÙ·ÁÚ·Ê‹˜ ÂÍ·ÚÙÒÌÂÓË ·fi ÙÔÓ ÈÛÙfi 77% ÔÌÔÏÔÁ›· Ì ÙÔÓ CXCR1 ˘Ô‰Ô¯¤· Ù˘ IL-8 (·ÁˆÁ‹ Û ̷ÎÚÔÊ¿Á·, ˈÛÈÓfiÊÈÏ·)
BLT1: ˘Ô‰Ô¯¤·˜ ÙÔ˘ Ï¢ÎÔÙÚÈÂÓ›Ô˘ LTB4
Ca2+i: ÂÓ‰Ô΢ÙÙ¿ÚÈÔ ·Û‚¤ÛÙÈÔ
cysLT1: ˘Ô‰Ô¯¤·˜ ÙˆÓ Î˘ÛÙÂÓ˘ÏÈÎÒÓ Ï¢ÎÔÙÚÈÂÓ›ˆÓ-1
G: ÚˆÙ½ÓË G
IL-8: ÈÓÙÂÚÏ¢ΛÓË-8
πƒ3: ÙÚÈʈÛÊÔÚÈ΋ ÈÓÔÛÈÙfiÏË
¿ÛıÌ· (14q11.2-13) (35). ŒÙÛÈ, Ë ˘ÂÚ¤ÎÊÚ·ÛË ÙÔ˘
LTB4 ÛÙË ÊÏÂÁÌÔÓ‹ (36-39) Î·È Ë ·Ú·Ù‹ÚËÛË fiÙÈ Ë
¤ÏÏÂÈ„Ë Ï¢ÎÔÙÚÈÂÓ›ˆÓ Û ÔÓÙÈÎÔ‡˜ Ô‰ËÁ› Û ·ÓÂ-
·Ú΋ ·¿ÓÙËÛË Û ÊÏÂÁÌÔÓÒ‰Ë ÂÚÂı›ÛÌ·Ù· (40) ‰ÈηÈÔÏÔÁÔ‡Ó ÙËÓ ·Ó¿Ù˘ÍË ·ÓÙ·ÁˆÓÈÛÙÒÓ ÙˆÓ BLT
˘Ô‰Ô¯¤ˆÓ ˆ˜ ·ÓÙÈÊÏÂÁÌÔÓˆ‰ÒÓ ·Ú·ÁfiÓÙˆÓ.
∂›Û˘, Ë Ô˘‰ÂÙÂÚÔÊÈÏ›· Ô˘ ÂÈ̤ÓÂÈ ÌÂÙ¿ ·fi ¯ÔÚ‹ÁËÛË ÎÔÚÙÈÎÔÛÙÂÚÔÂȉÒÓ ÔÊ›ÏÂÙ·È ÛÙËÓ ·Ó·ÛÙÔÏ‹ Ù˘ ·fiÙˆÛ˘ ÙˆÓ Ô˘‰ÂÙÂÚÔÊ›ÏˆÓ ÏfiÁˆ Ù˘ ·˘ÍË̤Ó˘ ÂÓ‰ÔÁÂÓÔ‡˜ Û‡ÓıÂÛ˘ ÙÔ˘ LTB4 (27). ∏ ÂÎÏÂÎÙÈ΋ ·Ó·ÛÙÔÏ‹ Ù˘ Û‡ÓıÂÛ˘ ÙÔ˘ LTB4 ‹ Ô ·ÔÎÏÂÈÛÌfi˜ ÙˆÓ ˘Ô‰Ô¯¤ˆÓ ÙÔ˘ ÌÔÚ› Ó·
∏πV-1 ‰ÂÓ ¤¯ÂÈ ·ÎfiÌË ÂȂ‚·Èˆı›, ·ÏÏ¿ ¤¯ÂÈ ˘ÔÛÙËÚȯı› fiÙÈ ·˘Ùfi˜ Èı·ÓÒ˜ Û˘ÌÌÂÙ¤¯ÂÈ ÛÙË ‰È·‰Èηۛ· ÂÈÛfi‰Ô˘ ÙÔ˘ ÈÔ‡ ÛÙ· ·ÙÙ·Ú· (19,43). ∆¤ÏÔ˜, ·Ó Î·È ÙÔ ÂӉȷʤÚÔÓ ÁÈ· Ù· Ï¢ÎÔÙÚȤÓÈ· ¤¯ÂÈ ÂÈÎÂÓÙÚˆı› ÛÙËÓ ÂÚÈʤÚÂÈ· ηÈ, Ì¿ÏÈÛÙ·, ÛÙÔ ÚfiÏÔ ÙÔ˘˜ ÛÙËÓ ·ıÔÊ˘ÛÈÔÏÔÁ›· ÙˆÓ ·ÙÔÈÎÒÓ ÓÔÛËÌ¿ÙˆÓ, ÂÓÙÔ‡ÙÔȘ, ÙfiÛÔ Ë ·Ú·ÁˆÁ‹ ÙÔ˘˜ fiÛÔ Î·È Ë ·ÚÔ˘Û›· ÛÈÙ¢ÙÈÎÒÓ Î˘ÙÙ¿ÚˆÓ ÛÙÔÓ ˘Ôı¿Ï·ÌÔ, ·ÏÏ¿ Î·È Ô ¯·Ú·ÎÙËÚÈÛÌfi˜ Ù˘ ·Ó¿ÚÎÂÈ·˜ Ù˘ Û‡ÓıÂÛ˘ ÙÔ˘ LTC4 ˆ˜ Ó¢ÚÔÌÂÙ·‚ÔÏÈ΋˜ ÓfiÛÔ˘ (44), ·ÓÔ›ÁÔ˘Ó Ó¤Ô˘˜ ÔÚ›˙ÔÓÙ˜ ÁÈ· ÙË ÌÂϤÙË
ÙÔ˘ ‚ÈÔÏÔÁÈÎÔ‡ ÚfiÏÔ˘ ÙˆÓ Ï¢ÎÔÙÚÈÂÓ›ˆÓ.
°ÂÓˆÌÈ΋ - º·ÚÌ·ÎÔÁÂÓˆÌÈ΋ ∆Ô ¿ÛıÌ· Â›Ó·È ÔχÏÔÎÔ Û‡Ó‰ÚÔÌÔ, ÛÙÔ ÔÔ›Ô ÁÂÓÂÙÈÎÔ› Î·È ÂÚÈ‚·ÏÏÔÓÙÈÎÔ› ·Ú¿ÁÔÓÙ˜
ηıÔÚ›˙Ô˘Ó ÙËÓ ·ÈÙÈÔÏÔÁÈ΋ ÂÙÂÚÔÁ¤ÓÂÈ· Î·È ÙË Ê·ÈÓÔÙ˘È΋ ¤ÎÊÚ·ÛË (45). ™‹ÌÂÚ·, Û¯ÂÙÈο ÌÂÁ¿ÏÔ˜
·ÚÈıÌfi˜ Ê·ÚÌ·ÎÔÁÂÓˆÌÈÎÒÓ ÌÂÏÂÙÒÓ ÂÛÙÈ¿˙ÂÈ ÛÙËÓ
Èı·Ó‹ Û˘ÌÌÂÙÔ¯‹ ÁÂÓÂÙÈÎÒÓ ÔÏ˘ÌÔÚÊÈÛÌÒÓ ÛÙË
·ıÔÊ˘ÛÈÔÏÔÁ›· ÙÔ˘ ¿ÛıÌ·ÙÔ˜ (35). ∏ ÔÈÎÈÏfiÙËÙ·
Ù˘ ·¿ÓÙËÛ˘ ÛÙ· ·ÓÙÈ·ÛıÌ·ÙÈο Ê¿Ú̷η Û˘Ì‚¿ÏÏÂÈ ÛÙËÓ ÔÏ˘ÏÔÎfiÙËÙ· Ù˘ Ê·Ú̷΢ÙÈ΋˜ ·ÓÙÈÌÂÙÒÈÛ˘ Ù˘ ÓfiÛÔ˘, ·ÊÔ‡ ÌÂÁ¿ÏÔ ÔÛÔÛÙfi Ù˘ ÌÂÙ·‚ÏËÙfiÙËÙ·˜ ‰È·ÊfiÚˆÓ ·Ú·Ì¤ÙÚˆÓ ÔÊ›ÏÂÙ·È ÛÙË ÁÂÓÂÙÈ΋ ÔÈÎÈÏfiÙËÙ· Î·È ÙÔÓ ÔÏ˘ÌÔÚÊÈÛÌfi ÙˆÓ ÁÔÓȉ›ˆÓ
(46,47).
ÚÔηϤÛÂÈ ·fiÙˆÛË ÙˆÓ Ô˘‰ÂÙÂÚÔÊ›ÏˆÓ Î·È ·Ó·ÛÙÔÏ‹ Ù˘ ‰Ú¿Û˘ ˘„ËÏÒÓ ‰fiÛÂˆÓ ÛÙÂÚÔÂȉÒÓ (27). ¶·Ú¿ÏÏËÏ·, Ë Û˘ÛÛÒÚ¢ÛË Î·È ÂÓÂÚÁÔÔ›ËÛË ÙˆÓ Ô˘‰ÂÙÂÚÔʛψÓ, ηıÒ˜ Î·È Ë ·ÂÏ¢ı¤ÚˆÛË ÙÔ˘ LTB4, ›Ûˆ˜ Û˘ÌÌÂÙ¤¯Ô˘Ó ÛÙËÓ ·ıÔÁ¤ÓÂÈ· Ù˘ ¯ÚfiÓÈ·˜ ·ÔÊÚ·ÎÙÈ΋˜ Ó¢ÌÔÓÔ¿ıÂÈ·˜, fiÔ˘ Ë ÙÔÈ΋ ÂÌÊ¿ÓÈÛË ÂÓfi˜ ¯ËÌÂÈÔÂÏÎÙÈÎÔ‡ Û‹Ì·ÙÔ˜ ÌÂÛÔÏ·‚› ÛÙËÓ ÚÔÛÎfiÏÏËÛË Î˘ÎÏÔÊÔÚÔ‡ÓÙˆÓ Ô˘‰ÂÙÂÚÔÊ›ÏˆÓ ÛÙÔ ÌÈÎÚÔ·ÁÁÂÈ·Îfi ÂÓ‰Ôı‹ÏÈÔ (41). ∏ ·ÓÔÛÔÏÔÁÈ΋ ‰Ú¿ÛË ÙÔ˘ LTB4 ÂÍ·ÚÙ¿Ù·È ·fi ÙÔÓ Ù‡Ô ÙÔ˘ ΢ÙÙ¿ÚÔ˘ Ô˘ ÂÓÂÚÁÔÔÈ› (20). ™Â Ê˘ÛÈÔÏÔÁÈΤ˜ Û˘Óı‹Î˜, ÙÔ LTB4 ·Ú¿ÁÂÙ·È Î˘Ú›ˆ˜ ÛÙ· Ô˘‰ÂÙÂÚfiÊÈÏ·, ÂÓÒ Î·Ù¿ ÙË ÊÏÂÁÌÔÓ‹ Û˘ÓÙ›ıÂÙ·È Î·È Û ¿ÏÏÔ˘˜ Ù‡Ô˘˜ ΢ÙÙ¿ÚˆÓ Ô˘ ‰È·ı¤ÙÔ˘Ó ˘‰ÚÔÏ¿ÛË ÙÔ˘ LTA4 (22). ™Ù· ˈÛÈÓfiÊÈÏ· ÚÔ¿ÁÂÈ ÙË ¯ËÌÂÈÔÙ·Í›·, ÂÓÂÚÁÔÔÈ› ÙËÓ ÔÍÂȉ¿ÛË Ù˘ NADPH Î·È ÙËÓ ¤ÎÊÚ·ÛË ÙˆÓ MAP ÎÈÓ·ÛÒÓ. ÀÂÚ¤ÎÊÚ·ÛË ÙÔ˘ LTB4 ¤¯ÂÈ ·Ó·ÊÂÚı› ÛÙËÓ „ˆÚ›·ÛË (36), ÙÔ ‚ÚÔÁ¯ÈÎfi ¿ÛıÌ· (37), ÙË ÚÂ˘Ì·ÙÔÂȉ‹ ·ÚıÚ›Ùȉ· (38), ÙËÓ ÂÏÎÒ‰Ë ÎÔÏ›Ùȉ· (39) Î·È ÙËÓ ÈÛ¯·ÈÌ›· (42). ∂›Û˘, Ë È‰ÈfiÙËÙ· ÙÔ˘ BLT1 ˆ˜ Û˘Ó˘Ô‰Ô¯¤· ÁÈ· ÙÔÓ Èfi Ù˘ ›ÎÙËÙ˘ ·ÓÔÛÔ·Ó¿ÚÎÂÈ·˜
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∏ÌÂÚÔÌËÓ›· ˘Ô‚ÔÏ‹˜: 22-03-2002
∏ÌÂÚÔÌËÓ›· ¤ÁÎÚÈÛ˘: 04-10-2002
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∏ÌÂÚ›‰· ·Ó¿ ‰ÈÂÙ›·: ¶ÚÒÙÔ˜ ·ÎÏÔ˜: 3 ÌfiÚÈ· ÁÈ· ¶·È‰›·ÙÚÔ˘˜ Î·È ¶·È‰ÔÓ¢ÌÔÓÔÏfiÁÔ˘˜ ¢Â‡ÙÂÚÔ˜ ·ÎÏÔ˜: 3 ÌfiÚÈ· ÌfiÓÔ ÁÈ· ¶·È‰ÔÓ¢ÌÔÓÔÏfiÁÔ˘˜
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ı· ‰ËÌÔÛȇÂÈ ÙÔÓ Î·Ù¿ÏÔÁÔ ÙˆÓ ÂÁÎÂÎÚÈ̤ӈÓ
™¶∂, ÒÛÙ ӷ Â›Ó·È ÚÔÛ·ÚÌÔṲ̂ÓÔ˜ ÛÙËÓ ÂοÛÙÔÙ ÂÈÎÚ·ÙÔ‡Û· ηٿÛÙ·ÛË.
O ¶Úfi‰ÚÔ˜ Ù˘ ∂ÏÏËÓÈ΋˜O ¶Úfi‰ÚÔ˜ Ù˘ ∂ÈÙÚÔ‹˜ ¶·È‰È·ÙÚÈ΋˜ ∂Ù·ÈÚ›·˜™˘Ó¯È˙fiÌÂÓ˘ ¶·È‰È·ÙÚÈ΋˜ ∂η›‰Â˘Û˘
∞Ó‰Ú¤·˜ °. ∫ˆÓÛÙ·ÓÙfiÔ˘ÏÔ˜¡ÈÎfiÏ·Ô˜ °. ªÂÚ¿Ù˘
µÈ‚ÏÈÔÁÚ·Ê›·
1. ªÂÚ¿Ù˘ ¡°, ∫ˆÓÛÙ·ÓÙfiÔ˘ÏÔ˜ ∞. ŒÓ·ÚÍË ÚÔÁÚ¿ÌÌ·ÙÔ˜ ™˘Ó¯È˙fiÌÂÓ˘ ¶·È‰È·ÙÚÈ΋˜ ∂η›‰Â˘Û˘ ˘fi ÙËÓ ∂ÏÏËÓÈ΋ ¶·È‰È·ÙÚÈ΋ ∂Ù·ÈÚ›·. ¶·È‰È·ÙÚÈ΋ 1999;62:508-510.
2. ªÂÚ¿Ù˘ ¡°, ª·Ï·Î¿-∑·ÊÂÈÚ›Ô˘ ∞. ¶ÚfiÁÚ·ÌÌ· ™˘Ó¯È˙fiÌÂÓ˘ ¶·È‰È·ÙÚÈ΋˜ ∂η›‰Â˘Û˘ ˘fi ÙËÓ ∂ÏÏËÓÈ΋ ¶·È‰È·ÙÚÈ΋ ∂Ù·ÈÚ›·. ¶·È‰È·ÙÚÈ΋ 2001;64:633-635.
3. D’ Apuzzo V, Helwig H, Siimes M. Charter on continuing medical education in paediatrics in the European Union. Eur J Pediatr 1998;157:192-193.
∫‡ÚÈ ∫ˆÓÛÙ·ÓÙfiÔ˘ÏÂ, ⁄ÛÙÂÚ· ·fi ÙȘ ‰È¢ÎÚÈÓÈÛÙÈΤ˜ Û·˜ ÂÈÛËÁ‹ÛÂȘ ÛÙË §¿ÚÈÛ· Î·È ÛÙËÓ ÂÙ‹ÛÈ· ıÂڷ¢ÙÈ΋ ÂÓË̤ڈÛË
Û¯ÂÙÈο Ì ÙÔ ÂÌ‚fiÏÈÔ Ù˘ ÔÏÈÔÌ˘ÂÏ›Ùȉ·˜, Ô Î¿ı ÂÓËÌÂڈ̤ÓÔ˜ ·È‰›·ÙÚÔ˜ ÁÓˆÚ›˙ÂÈ Ï¤ÔÓ ÙÔ ÚÔÙÂÈÓfi-
ÌÂÓÔ Û¯‹Ì· ‹ Ì¿ÏÏÔÓ Ù· ÚÔÙÂÈÓfiÌÂÓ· Û¯‹Ì·Ù· ÁÈ· Ù· ÂÓۈ̷و̤ӷ Ì ¿ÏÏ· ÂÌ‚fiÏÈ· ÂÓ·›ÛÈÌ· ÂÌ‚fiÏÈ·
ÔÏÈÔÌ˘ÂÏ›Ùȉ·˜ Î·È ÙȘ ÂÚÈÔÚÈṲ̂Ó˜ ϤÔÓ ÂӉ›ÍÂȘ ÙÔ˘ ÂÌ‚ÔÏ›Ô˘ Sabin. ∂ÓÙÔ‡ÙÔȘ, Ë ÂÙ·ÈÚ›· µπ∞¡∂•, Ë ÔÔ›· ÂÍ·ÎÔÏÔ˘ı› Ó· ÂÈÛ¿ÁÂÈ ÙÔ ÂÌ‚fiÏÈÔ Sabin Ì ‚Ú·¯‡ ¯ÚfiÓÔ ËÌÂÚÔÌËÓ›· Ï‹Í˘ ¤¯ÂÈ ÛËÌÂÈÒÛÂÈ Î·Ù’ ·ӿÏË„ÈÓ ÂÏÏ›„ÂȘ, ÙȘ Ôԛ˜ Ù›ÓÂÈ Ó· Û˘ÌÏËÚÒÛÂÈ Ë ÂÙ·ÈÚ›· °ÂÚÔÏ˘Ì¿ÙÔ˘ Ì ÙÔ ÂÌ‚fiÏÈÔ POLYORAL. ∞ÚÎÂÙÔ› ÂÎ ÙˆÓ Û˘Ó·‰¤ÏÊˆÓ ÙÔ ¯ÚËÛÈÌÔÔÈÔ‡Ó, ·Ó Î·È ÙÔ Ï›ÛÙÔ ÙÔ ÂÌ‚ÔÏ›Ô˘ ·Ú·Ì¤ÓÂÈ ÚÔÛÚÔÊË̤ÓÔ Â› ÙˆÓ ÙÔȯˆÌ¿ÙˆÓ ÙÔ˘ Ï·ÛÙÈÎÔ‡ ÊÈ·Ïȉ›Ô˘ ÌÂÙ¿ ·fi ÙËÓ ÂÎΤӈۋ ÙÔ˘, Ì ·ÔÙ¤ÏÂÛÌ· ÙÔ ÂÌ‚ÔÏÈ·˙fiÌÂÓÔ ‚Ú¤ÊÔ˜ Ó· Ï·Ì‚¿ÓÂÈ ÙÂÏÈο ÌÈÎÚfi ÙÌ‹Ì· Ù˘ ‰fiÛˆ˜. ∂Âȉ‹ Ë ÔÏÈÔÌ˘ÂÏ›ÙȘ ·Ú·Ì¤ÓÂÈ ÛÙË
ÌÓ‹ÌË ÙˆÓ ÂÚÈÛÛfiÙÂÚˆÓ, ȉ›ˆ˜ ·Ï·ÈÒÓ ·È‰È¿ÙÚˆÓ, ˆ˜
18-02-2003
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∫‡ÚÈ ¶ÂÚÚ¿ÎË, ™˘ÌʈÓÒ ·fiÏ˘Ù·
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