Tetrahydrobiopterin sensitivity in German patients with mild phenylalanine hydroxylase deficiency

We report the results of tetrahydrobiopterin (BH 4 ) loading tests in 10 German patients with mild phenylketonuria. A significant decline of phenylalanine values after application of BH 4 was observed in all but one patients. Molecular genetic analyses revealed a range of different PAH gene mutations. Re‐testing of one patient previously reported as non‐responsive to BH 4 loading showed a moderate response with a higher dose of BH 4 . Nevertheless, there appear to be kinetic differences in phenylalanine hydroxylation in patients with the same genotype. Non‐responsiveness to 20 mg/kg BH 4 was observed only in a single patient who was compound heterozygous for the novel mutation R176P (c.527G>C) and the common null‐mutation P281L. In summary, our data are in line with recent reports indicating that BH 4 sensitivity is a normal feature of most mild forms of PAH deficiency but may be influenced by other factors. © 2003 Wiley‐Liss, Inc.