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Effects and clinical significance of tetrahydrobiopterin supplementation in phenylalanine hydroxylase‐deficient hyperphenylalaninaemia
Author(s) -
Gramer G.,
Burgard P.,
Garbade S. F.,
Lindner M.
Publication year - 2007
Publication title -
journal of inherited metabolic disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 102
eISSN - 1573-2665
pISSN - 0141-8955
DOI - 10.1007/s10545-007-0651-6
Subject(s) - hyperphenylalaninemia , phenylalanine hydroxylase , tetrahydrobiopterin , phenylalanine , medicine , clinical significance , pediatrics , endocrinology , chemistry , biochemistry , nitric oxide synthase , amino acid , nitric oxide
Summary In recent years several studies on tetrahydrobiopterin (BH 4 )‐responsive phenylalanine hydroxylase (PAH) deficiency have been published. The molecular mechanisms of BH 4 responsiveness are not conclusively understood, but there is evidence that BH 4 responsiveness in hyperphenylalaninaemia (HPA) depends on the patient's genotype and residual PAH activity. As a BH 4 preparation will soon obtain marketing approval as an alternative treatment for phenylketonuria (PKU), it is particularly important to evaluate this treatment and to define criteria to identify patients with a potential benefit from it. Most of the patients found to be BH 4 ‐responsive suffered from mild PKU or mild hyperphenylalaninaemia (MHP) and some of these would not be treated at all in many countries. Of patients with moderate and classic forms of PKU, only a few were classified as responders and the clinical significance of the effect size may be small.