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Tetrahydrobiopterin Responsiveness in Phenylketonuria. Two New Cases and a Review of Molecular Genetic Findings
Author(s) -
Lässker U.,
Zschocke J.,
Blau N.,
Santer R.
Publication year - 2002
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:1015194002487
Subject(s) - tetrahydrobiopterin , human genetics , metabolic disease , phenylalanine hydroxylase , medicine , endocrinology , hyperphenylalaninemia , genetics , biology , phenylalanine , gene , nitric oxide synthase , amino acid , nitric oxide
We report two new patients with tetrahydrobiopterin (BH 4 )‐responsive phenylketonuria and compare their phenylalanine hydroxylase (PAH) genotypes (A395P/IVS12+1g>a and R261Q/I65T, respectively) to those of previous cases from the literature. These case observations confirm earlier reports stating that BH 4 ‐responsive patients are frequently carriers of a missense mutation within the DNA region coding for the catalytic domain of the enzyme. Interestingly, many of the PAH gene mutations detected in BH 4 ‐responsive patients have been associated with an inconsistent phenotype in the past. Our case reports confirm that it is necessary to thoroughly examine individuals with increased phenylalanine levels, not only to detect BH 4 deficiency, but also to identify patients with PAH deficiency who may benefit from BH 4 treatment. In both of our patients, however, an effect of BH 4 (7.5 mg/kg) on plasma phenylalanine levels was not seen in the newborn period. We therefore conclude that a normal neonatal BH 4 test does not necessarily exclude BH 4 responsiveness in all such patients.