In Vivo Studies of Phenylalanine Hydroxylase by Phenylalanine Breath Test: Diagnosis of

ylase (PAH) deficiency is characterized by reduction of blood phenylalanine level after a BH4-loading test. Most cases of BH4-responsive PAH deficiency include mild phenylketonuria (PKU) or mild hyperphenylalaninemia (HPA), but not all pa-tients with mild PKU respond to BH4. We performed the phe-nylalanine breath test as reliable method to determine the BH4 responsiveness. Phenylalanine breath test quantitatively mea-sures the conversion of L-[1-13C] phenylalanine to 13CO2 and is a noninvasive and rapid test. Twenty Japanese patients with HPA were examined with a dose of 10 mg/kg of 13C-phenylalanine with or without a dose of 10 mg · kg1 · d1 of BH4 for 3 d. The phenylalanine breath test [cumulative recovery rate (CRR)] could distinguish control subjects (15.4 1.5%); heterozygotes (10.3 1.0%); and mild HPA (2.74%), mild PKU (1.13 0.14%), and classical PKU patients (0.29 0.14%). The geno