FOCUS ON PKU
Rachel Wilson RD Clinical Science Dietitian, Vitaflo International Ltd After seven years in the NHS, nearly four years within IEM, Rachel joined Vitaflo in January 2017 where she now develops education literature, study events and clinical trials. Written in collaboration with: Charlotte Ellerton RD, Metabolic Dietetic Practitioner, Charles Dent Metabolic Unit, UCLH Charlotte has been working in IEM for nearly nine years. She is particularly interested in pregnancy in IEM and diabetes. Current research areas include maternal PKU and glycogen storage disorders.
REFERENCES For full article references please CLICK HERE . . .
UNPLANNED PREGNANCY IN WOMEN WITH PHENYLKETONURIA (PKU): A DIETETIC EMERGENCY The aim of this article is to provide a summary of PKU and its management during preconception and pregnancy, known as maternal PKU (mPKU), and to offer guidance on how to dietetically manage an individual with PKU who is planning a pregnancy, or is pregnant. Expert dietetic advice is essential for the management of PKU during preconception and pregnancy. High levels of phenylalanine (Phe) levels are teratogenic, and can result in irreversible physical and cognitive damage of the foetus.1,2 From a young age, females with PKU are taught about the need for a strict PKU diet when they are ready to have a baby of their own. As with many people with chronic conditions, individuals with PKU can struggle to attend outpatient clinics, adhere to medical and dietary advice (particularly as teenagers and young adults), and may become lost to follow-up to the specialist metabolic services.3,4 These individuals can present to their general practitioner (GP) when planning, or upon discovery of, a pregnancy. Their GP may refer these individuals to their local dietetic service for specialist dietary advice. If you received such a referral, would you know what to do? WHAT IS PKU?
PKU is an inborn error of Phe metabolism. Without early dietary management, the amino acid Phe and its metabolites accumulate to toxic levels, and cause progressive and irreversible neurological impairment.5 PKU effects approximately one in 10,000 people in the UK. It was the first
metabolic condition to be targeted by newborn screening (NBS) in the UK in the late 1960s. Individuals identified and managed following NBS can expect to grow and develop similarly to their peers, attend mainstream schools, graduate from University, and live independently with jobs and families of their own.5 MANAGEMENT OF PKU
PKU is managed with individualised dietary advice to achieve and maintain target Phe levels and optimal nutritional intakes. Dietary management requires: • a severe restriction of all dietary protein- requiring prescription-only low protein (LP) foods to provide energy, bulk and variety; • a prescription of protein substitutes (PS) - these contain all the other amino acids except Phe and most also contain micronutrients that would otherwise be insufficient in a protein restricted diet, including iron, vitamin B12, calcium, iodine, vitamin D, zinc and DHA. Target Phe levels:5 • 120-360µmol/L from birth to 12 years • 120-600µmol/L from 13 years onwards • 120-360µmol/L during preconception and pregnancy www.NHDmag.com May 2018 - Issue 134
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FOCUS ON PKU Figure 1. Dysmorphic features which are related to maternal PKU syndrome
mother’s Phe is uncontrolled during pregnancy, the foetus is exposed to amplified levels. The damage to the foetus resulting from high Phe levels is greater than that caused by undiagnosed and untreated PKU8 and is believed to be comparable to foetal alcohol syndrome.9 Thankfully, maternal PKU syndrome can be avoided with diligent dietary management prior to conception and during pregnancy,5 and many women with PKU who are managed with specialist care have healthy babies.
Until the 1980s, it was usual clinical practice to discontinue the PKU diet during childhood, as it was thought that the brain is sufficiently developed by age eight or 10 and so no longer benefits from supressed Phe levels.6 Some adults with PKU will have relaxed, or discontinued their diet and may no longer attend regular metabolic clinic appointments. It is now considered that Phe levels should be controlled throughout life for best outcomes for individuals with PKU.5 Newly published European guidelines5 recommend that all children and adults with PKU are managed within a specialist metabolic centre, by experienced physicians, dietitians and multidisciplinary teams (MDT). MANAGEMENT OF MATERNAL PKU
Exposure of a foetus to elevated levels of Phe causes physical and cognitive problems, and results in maternal PKU syndrome.1 Symptoms of maternal PKU syndrome include: • microcephaly • intellectual disability • behavioural problems • restricted foetal growth • low birth weight • cognitive heart defects (CHD) • dysmorphic features (which are shown in Figure 1) Due to a positive amino acid gradient across the placenta, the foetus is exposed to a higher Phe concentration than the mother.7 When the
The best outcomes for children born to mothers with PKU are reported when their Phe level is controlled prior to conception, referred to as a ‘planned pregnancy’.10,11 The foetus is fully formed by the 12th week of pregnancy and the heart is formed by the 10th week, so this is an important time to protect the foetus from high Phe levels. Most women will not know they are pregnant until they miss their first or their second period, which relates to the fourth or eighth week of pregnancy. When conception occurs with uncontrolled Phe levels in an ‘unplanned pregnancy’, more favourable birth outcomes are reported if the Phe level is between 120 and 360μmol/L at the earliest possible point, with eight to 10 weeks gestation being a critical time point.2 Dietary restriction should commence immediately in an ‘unplanned pregnancy’ for the best possible outcomes. It is vital that an individual with PKU who finds out she is pregnant makes contact with a specialist metabolic centre as quickly as possible for specialist advice. Dietary management for a PKU pregnancy should be overseen in a specialist metabolic centre experienced in the care of mPKU.5,10. Care is required from a MDT, including a physician, dietitian and, ideally, a psychologist, who are all specialised in the management of adults with inborn errors of metabolism (IEM).5 There are 10 metabolic centres in the UK who provide specialist care for pregnant women with PKU. Their contact details can be found via the National Society for Phenylketonuria (NSPKU) website under ‘emergency contacts’. www.NHDmag.com May 2018 - Issue 134
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FOCUS ON PKU CASE STUDY Alice is 26 years old with PKU. She was lost to follow up from the metabolic services at 17 years-of-age after her attendance with the paediatric metabolic services deteriorated. She was referred to the adult metabolic clinic, but never attended her transition appointments. Her adherence to the low protein diet and protein substitute had been declining from the age of 14 and by aged 17 she had stopped taking her protein substitutes completely and discontinued blood monitoring. She had also stopped eating low protein foods and ate small amounts of dairy and grains daily, and meat on a few days a week. Figure 2: Timeline for Alice within the metabolic service HCP contact: Alice attended a GP appointment to inform them that she would like to start a family. She knew she needed to plan with PKU. Weight: 46.2kg Height: 1.62m BMI: 17.2kg/m2
HCP contact: Referral received by dietetic department.
HCP contact: GP surgery received declined referral and placed in GP intray.
HCP contact: Paediatric metabolic dietitian received referral.
HCP contact: UCLH metabolic dietitian called Alice who reported she had recently taken a positive pregnancy test and thought she was 4-6 weeks pregnant.
04 July '16
19 July '16
12 August '16
26 August '16
26 August '16
Action: 1. Referred to local hospital dietetic outpatient service by letter. 2. Arranged for her contraceptive coil to be removed. 3. Advised to start 400µg folic acid daily.
29 July '16
18 August '16
26 August '16
Action: Dietetic service declined referral. Wrote to GP with covering letter explaining reason for inappropriate referral was that they could not provide advice on management of PKU during pregnancy.
Action: GP wrote to local metabolic clinic for advice.
Action: Paediatric metabolic dietitian immediately rang adult metabolic service (UCLH) to inform team of PKU patient needing preconception advice.
Action: Metabolic dietitian provided dietary advice over the phone, booked clinic appointment with metabolic service for following Monday, arranged for emergency deliveries of protein substitute and LP foods with next day delivery.
Despite knowing that she needed to plan her pregnancy in PKU, Alice was not able to rapidly access the correct service to support her with dietary management of mPKU prior to conception. When Alice was contacted by the metabolic service, she was very anxious and concerned about her baby. The mPKU diet was initiated quickly, which meant that her Phe level reached target range by seven weeks gestation minimising the risk of the foetus being affected by maternal PKU syndrome. Although the best possible outcomes for the infant are associated with the mPKU diet being initiated prior to conception, good outcomes are reported when metabolic control is achieved by 10 week’s gestation and maintained throughout pregnancy. Alice was counselled by the metabolic consultant and decided to continue with the pregnancy. Alice was highly motivated and adhered very well to advice and monitoring. Detailed anomaly scans were conducted at 20 weeks gestation and no structural abnormalities were identified for the baby’s heart, and the growth and development were reported to be normal. Her baby boy was born at term. He was tested for PKU on Day 5 through routine neonatal screening and the results were negative. Head circumference was on the 25th centile and there were no immediate signs of maternal PKU syndrome. Alice’s baby will be offered neuropsychological assessments at 18 months, four and eight years of age which are organised by her metabolic unit for outcome monitoring. So far, the outcome for Alice’s infant appears to be good; however, the delays in accessing the correct service and conceiving before metabolic control was achieved was very distressing for Alice, requiring emergency management from the metabolic team and could easily have been prevented. Alice is now enjoying motherhood and attends yearly followup appointments at the metabolic clinic. She hopes to plan for a second pregnancy in the future. What to do if you receive a referral for a patient with PKU who is planning a pregnancy, or who is already pregnant:
• ACT IMMEDIATELY - ideally within an hour of receiving the referral. • Call your nearest metabolic centre at the first opportunity. - Visit the NSPKU website, click the 'Contact' tab, and then choose 'Emergency Contacts'. • Emphasise the referral is for mPKU so that it can be appropriately prioritised by the metabolic unit. • Provide the metabolic unit with as much information as possible. • Advise the original referrer of your actions.
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