IN ASSOCIATION WITH THE NSPKU
PHENYLALANINE NEUROTOXICITY AND THE CHALLENGE OF ‘DIET FOR LIFE’* IN PKU Lifelong phenylalanine (Phe) restriction, with intake of protein substitutes, is essential for the prognosis of PKU, but is burdensome, considerably demanding and often difficult to follow. This article looks at the mechanisms for brain damage in PKU and outlines some of the evidence supporting ‘Diet for Life’. Phenylketonuria (PKU) is a rare autosomal disorder of phenylalanine (Phe) metabolism. It was first discovered in 1934 and occurs due to inherited mutations in the gene encoding Phe hydroxylase. Lifelong Phe restriction and intake of protein substitutes are both essential, yet demanding and often difficult to follow. Consequently, many patients stop following the PKU diet and may also become disengaged from metabolic review. Furthermore, non-metabolic dietitians may discover patients with PKU who have been ‘lost to follow-up’ and have been referred into other dietetic caseloads. Irrespective of their discovery, it is important that these patients are offered metabolic specialist input to facilitate a return to diet, or, at the very least, provided with robust scientific evidence so they can make informed choices about being off diet and the chance to be under detailed nutritional scrutiny by metabolic dietitians and other members of the multidisciplinary metabolic team. WHAT IS THE PATHOPHYSIOLOGY AND MANAGEMENT OF PKU?
PKU is characterised by disrupted catabolism of Phe into tyrosine and its metabolites. The metabolites of tyrosine act as precursors of several neurotransmitters, catecholamines and hormones, including dopamine, norepinephrine, epinephrine, thyroxine and melanin. Without appropriate management, Phe accumulates in the blood and becomes neurotoxic.
For the unmanaged or poorly managed individual, chronically elevated Phe manifests in a spectrum of progressive and irreversible neuroanatomical and neurophysiological disturbances. With the introduction of newborn screening, PKU became the first metabolic disorder identifiable in the absence of clinical symptoms. Early identification (via newborn screening) and immediate (before 10-14 days of age) dietary intervention is essential for the prognosis of this disorder, whereby patients can achieve almost normal clinical outcome in comparison to their non-PKU counterparts if blood Phe concentrations are maintained at a necessary level. WHAT IS THE CURRENT ADVICE FOR PATIENTS?
PKU management is by way of a lowprotein diet and intake of protein substitutes virtually devoid of Phe. The PKU diet is well established, safe and effective and, consequently, remains the cornerstone of PKU management and has been since its conception in 1953. The duration and stringency of Phe restriction necessary to avert the metabolic consequences of PKU, has been the centre of controversy for decades. Historically, lifelong Phe restriction was generally unsupported. Many practitioners assumed that the diet could be discontinued from age six with no adverse effect.1,2 This practice was fuelled by the belief that elevated Phe is only neurotoxic during periods of growth, development and maximal myelinisation (the development of a protective
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Suzanne Ford RD Dietetic Team Leader, Bristol Southmead Hospital; Society Dietitian (Adults), The National Society for Phenylketonuria
Dr Ben Green PhD Medical Affairs Research Advisor, Nutricia Advanced Medical Nutrition
REFERENCES Please visit the Subscriber zone at NHDmag.com
www.NHDmag.com May 2019 - Issue 144
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