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The tetrahydrobiopterin loading test in 36 patients with hyperphenylalaninaemia: Evaluation of response and subsequent treatment
Author(s) -
Bóveda M. D.,
Couce M. L.,
Castiñeiras D. E.,
Cocho J. A.,
Pérez B.,
Ugarte M.,
Fraga J. 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/s10545-007-0567-1
Subject(s) - phenylalanine hydroxylase , tetrahydrobiopterin , hyperphenylalaninemia , phenylalanine , medicine , phenylketonurias , endocrinology , population , pediatrics , chemistry , biochemistry , amino acid , nitric oxide synthase , environmental health , nitric oxide
Summary The response to tetrahydrobiopterin (BH 4 ) in patients with phenylalanine hydroxylase (PAH, EC 1.14.16.1) deficiency (OMIM 261600) has been widely reported. Here we report results of the BH 4 loading test (20 mg/kg per day) in a group of 36 patients with PAH deficiency and phenotype of mild hyperphenylalaninaemia (HPA), mild phenylketonuria (PKU) or classic PKU. The patients ranged from neonates aged 7–15 days, detected in the Newborn Screening Programme for PKU in the population of Galicia (NW Spain), to adults aged up to 32 years who had been receiving a low‐phenylalanine (Phe) diet for a period of years. Ten of the 36 patients showed a reduction of more than 30% in plasma Phe levels within 24 h of BH 4 loading (ranging from 33.7% to 90.2%, mean 59.2%, SD 19.8%). All the patients with mild HPA (100%) showed a positive response; 57% of patients with mild PKU (4 of 7) showed a positive response. Of particular interest were positive responses in two patients with classic PKU, and in one patient with mutations of the phenylalanine hydroxylase (PAH) gene that have not to date been reported to be BH 4 ‐responsive (p.S303A and p.G46S). BH 4 treatment (5–8 mg/kg per day) was commenced in 9 of the 10 BH 4 ‐responsive patients. The observed responses to treatment argue for application of the BH 4 loading test in all patients with HPA or PKU, independently of genotype, phenotype or age.