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Tetrahydrobiopterin‐responsive phenylalanine hydroxylase deficiency in Dutch neonates
Author(s) -
Spaapen L. J. M.,
Bakker J. A.,
Velter C.,
Loots W.,
RubioGonzalbo M. E.,
Forget P. P.,
Dorland L.,
De Koning T. J.,
PollThe B. T.,
Ploos Van Amstel H. K.,
Bekhof J.,
Blau N.,
Duran M.
Publication year - 2001
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 - 10.1023/a:1010596317296
Subject(s) - tetrahydrobiopterin , phenylalanine , hyperphenylalaninemia , phenylalanine hydroxylase , biopterin , endocrinology , medicine , basal (medicine) , concomitant , chemistry , enzyme , cofactor , biochemistry , amino acid , insulin
Four neonates with a positive phenylalanine screening test (Phe concentrations between 258 and 1250 μmol/L) were investigated further to differentiate between phenylalanine hydroxylase (PAH) deficiency and variant hyperphenylalaninaemia (HPA) forms. In patients 1 and 2 a tetrahydrobiopterin (BH 4 ) load caused a significant decrease of the plasma Phe levels. A combined phenylalanine/BH 4 loading test was performed in patients 2, 3 and 4. In the latter two patients, plasma Phe concentrations completely normalized within 8 h after the BH 4 load (20 mg/kg). Basal urinary pterins were normal in all four patients. The activity of dihydropteridine reductase (DHPR) was normal in patients 1, 2 and 3 and 50% of control values in patient 4 (not in the range of DHPR‐deficient patients). In patient 3 a subsequent phenylalanine loading test with concomitant analysis of plasma biopterins revealed a normal increase of biopterin, excluding a BH 4 biosynthesis defect. Pterins and neurotransmitter metabolites in CSF of patients 1, 3 and 4 were normal. DNA mutations detected in the PAH gene of patients 1–4 were A313T, and L367fsinsC; V190A and R243X; A300S and A403V; R241C and A403V. The results are suggestive for mutant PAH enzymes with decreased affinity for the cofactor BH 4 .