Phenylketonuria (PKU): A problem solved?

Christine S Brown,Uta Lichter-Konecki

doi:10.1016/j.ymgmr.2015.12.004

Christine S Brown, Uta Lichter-Konecki

Open Access

https://doi.org/10.1016/j.ymgmr.2015.12.004

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Abstract

Phenylketonuria (PKU) is a rare metabolic disorder characterized by impaired conversion of phenylalanine (Phe) to tyrosine. If left untreated, the resultant accumulation of excess blood Phe can cause physiological, neurological, and intellectual disabilities. The National PKU Alliance (NPKUA) conducted a survey of its membership to assess current health status and interest in new treatments for PKU. Of the 625 survey respondents, less than half (46.7%) reported blood Phe within (120–360μmol/L) — the range recommended by the American College of Medical Genetics and Genomics (ACMG). The survey results also showed that younger (≤18years) individuals were about 3-times as successful in keeping their blood Phe concentrations within the recommended clinical range compared with adults. Blood Phe over 360μmol/L was reported in one-quarter (25.5%) of ≤18year old individuals and almost two-thirds (61.5%) of adults. A little more than half (51.7%) of respondents reported having difficulty in managing their PKU, including the maintenance of a Phe-restricted diet. Individuals with PKU desire new treatments that would allow them to increase their intake of natural protein, discontinue or reduce their intake of medical foods (medical formula and foods modified to be low in protein), improve their mental health (including a reduction in depression and anxiety), and a reduction of their blood Phe concentrations. Respondents preferred oral administration of any newly developed therapies and, in general, disliked therapeutic injections. Injections at home were preferred over injections at a clinic. Payers, government agencies, clinicians, and industry partners should consider patient input when developing and approving new therapies and treatments for PKU.

Highlights

Phenylketonuria [PKU, MIM 261600, referred to as phenylalanine hydroxylase (PAH; EC 1.14.16.1) deficiency] is a rare autosomal recessive disorder characterized by an impairment of the body's ability to metabolize phenylalanine (Phe) [1]
Pharmaceutical treatments include the use of sapropterin dihydrochloride (a synthetic form of tetrahydrobiopterin (BH4) — the natural co-factor for the PAH enzyme)
Studies have shown that sapropterin dihydrochloride is well tolerated, lowers blood Phe, and improves Phe tolerance in approximately 25–50% of individuals with PKU [2,5]

Summary

Introduction

Phenylketonuria [PKU, MIM 261600, referred to as phenylalanine hydroxylase (PAH; EC 1.14.16.1) deficiency] is a rare (prevalence b 1/10,000–1/15,000 births) autosomal recessive disorder characterized by an impairment of the body's ability to metabolize phenylalanine (Phe) [1]. Without a fully functional PAH enzyme, Phe accumulates in the blood, brain, and body tissues. The new treatment guidelines of the American College of Medical Genetics and Genomics (ACMG) state that the clinical treatment goal for individuals with PKU are to maintain blood Phe within the range of (120–360 μmol/L) for individuals of all ages and that treatment should be lifelong [2]. Dietary treatment [including the use of Phe-free medical foods and the avoidance of high protein foods] successfully lowers blood Phe in most individuals with PKU [4]. Pharmaceutical treatments include the use of sapropterin dihydrochloride (a synthetic form of tetrahydrobiopterin (BH4) — the natural co-factor for the PAH enzyme). Studies have shown that sapropterin dihydrochloride is well tolerated, lowers blood Phe, and improves Phe tolerance in approximately 25–50% of individuals with PKU [2,5]

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