title: Tetrahydrobiopterin sensitivity in German patients with mild phenylalanine hydroxylase deficiency.
abstract: We report the results of tetrahydrobiopterin (BH4) loading tests in 10 German patients with mild phenylketonuria. A significant decline of phenylalanine values after application of BH4 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 BH4 loading showed a moderate response with a higher dose of BH4. Nevertheless, there appear to be kinetic differences in phenylalanine hydroxylation in patients with the same genotype. Non-responsiveness to 20 mg/kg BH4 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 BH4 sensitivity is a normal feature of most mild forms of PAH deficiency but may be influenced by other factors.
authors.affiliation: Division of Metabolic and Endocrine Disorders, University Children's Hospital, Heidelberg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Lindner
authors.forename: R
authors.initials: R
authors.lastname: Steinfeld
authors.forename: P
authors.initials: P
authors.lastname: Burgard
authors.forename: A
authors.initials: A
authors.lastname: Schulze
authors.forename: E
authors.initials: E
authors.lastname: Mayatepek
authors.forename: J
authors.initials: J
authors.lastname: Zschocke
mesh_terms: D000284:Administration, Oral; D019943:Amino Acid Substitution / Q000235:genetics / Q000502:physiology; D001708:Biopterins / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism*; D002648:Child; D004334:Drug Administration Schedule; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D020125:Mutation, Missense / Q000235:genetics; D015997:Neonatal Screening; D010649:Phenylalanine / Q000097:blood; D010651:Phenylalanine Hydroxylase / Q000172:deficiency* / Q000502:physiology; D010661:Phenylketonurias / Q000097:blood / Q000201:enzymology* / Q000378:metabolism
chemical_list: D001708:Biopterins; D010649:Phenylalanine; D010651:Phenylalanine Hydroxylase; C003402:sapropterin