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Tetrahydrobiopterin-responsive hyperphenylalaninemia/ phenylketonuria (BH4-responsive hyperphenylalaninemia/ phenylketonuria) is a form of phenylketonuria (PKU, see this term), an inborn error of amino acid metabolism, characterized by mild to moderate symptoms of PKU including impaired cognitive function, seizures, and behavioral and developmental disorders, and a marked reduction and normalization of elevated phenylalanine concentrations after oral loading with tetrahydrobiopterin (BH4; sapropterin dihydrochloride), an essential cofactor of phenylalanine hydroxylase.
ORPHA:293284Classification level: Subtype of disorder
- BH4-responsive HPA/PKU
- BH4-responsive hyperphenylalaninemia/phenylketonuria
- Tetrahydrobiopterin-responsive HPA/PKU
- Prevalence: Unknown
- Inheritance: Autosomal recessive
- Age of onset: Infancy, Neonatal
- ICD-10: E70.1
- OMIM: -
- UMLS: -
- MeSH: -
- GARD: -
- MedDRA: -
Prevalence of this form of PKU is not known but a significant proportion (10-30%) of patients with PKU may benefit from therapy with BH4.
Patients with mild to moderate symptoms of PKU can be identified as BH4-responsive following oral loading with 20 mg/kg/day of sapropterin dihydrochloride if a significant reduction in Phe levels is observed after 24-48 hours of treatment. An efficacy test (20 mg/kg/day) over several weeks should confirm initial responsiveness.
BH4-responsive HPA/PKU is caused by specific mutations (coding for mutant proteins with significant residual activity) in the PAH gene (12q22-q24.2) encoding the phenylalanine hydroxylase enzyme.
Transmission is autosomal recessive.
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