Long-Term Treatment and Diagnosis of Tetrahydrobiopterin-Responsive Hyperphenylalaninemia with a Mutant

A novel therapeutic strategy for phenylketonuria (PKU) has been initiated in Japan. A total of 12 patients who met the criteria for tetrahydrobiopterin (BH4)-responsive hyperphenylalaninemia (HPA) with a mutant phenylalanine hydroxylase (PAH) (EC 1.14.16.1) gene were recruited at 12 medical centers in Japan between June 1995 and July 2001. Therapeutic efficacy of BH4 was evaluated in single-dose, four-dose, and 1-wk BH4 loading tests followed by long-term BH4 treatment, and also examined in relation to the PAH gene mutations. The endpoints were deter-mined as the percentage decline in serum phenylalanine from initial values after single-dose (20%), four-dose (30%), and 1-wk BH4 (50%) loading tests. Patients with mild PKU exhib-iting decreases in blood phenylalanine concentrations of 20% in the single-dose test also demonstrated decreases of 30 % in the four-dose test. The 1-wk test elicited BH4 responsivenes