Mutations in the Regulatory Domain of Phenylalanine Hydroxylase and Response to Tetrahydrobiopterin

Tetrahydrobiopterin (BH4) is a co-factor that enhances the activity of other enzymes, and this co-factor level is found to be affected in phenylketonuria (PKU), an amino acid metabolism disorder. The present study was aimed at understanding the effect of BH4 on mutations in the regulatory domain of phenylalanine hydroxylase (PAH). Among 14 patients, 5 patients were classical PKU, 3 were atypical PKU, and 6 were mild PKU. All of these patients had at least one mutation in the regulatory domain. Patients were given 10 mg/kg BH4, and the response of blood phenylalanine (Phe) levels was monitored following treatment. The level of blood Phe decreased after BH4 treatment in all of the patients. These studies suggest that mutations in the regulatory domain also responded to BH4 even if the patient had classical PKU.