Identification of mutations causing 6-pyruvoyl-tetrahydrobiopterin synthase deficiency in Polish patients with variant hyperphenylalaninemia

Background: 6-Pyruvoyl-tetrahydrobiopterin synthase (PTPS) is required for biosynthesis of tetrahydrobiopterin, the cofactor of various enzymes includ ing the hepatic phenylalanine hydroxylase. Mutations in the PTS gene result in a variant type of hyperphenylalaninemia, requiring cofactor replacement therapy for treatment. Methods and Results: Four Polish patients with PTPS deficiency were screene d for mutations in the PTS gene. Three novel mutations E35G, N36K, and F100 V were identified. In one patient, a known mutation D136V was identified in both PTS alleles. Conclusions: Mutation D136V present in both alleles was proposed to be conn ected with a mild form of PTPS deficiency. The other three mutations were f ound in heterozygous patients with a central type of PTPS deficiency. D136V mutation is a common mutation in the Polish population.