Early Diagnosis of 6-Pyruvoyl-tetrahydropterin Synthase Deficiency

Abstract

Summary 6-Pyruvoyl-tetrahydropterin synthase (PTPS) deficiency, which used to be called dihydrobiopterin synthase deficiency, is the most common kind of tetrahydrobiopterin deficiency. Early treatment by administration of tetrahydrobiopterin and neurotransmitter precursors helps to prevent neurological injury, so prompt diagnosis of neonates with hyperphenylalaninemia discovered by screening for phenylketonuria is necessary. Three patients with PTPS deficiency were diagnosed by pteridine analysis. All patients had low biopterin and high neopterin levels in the urine, resulting in a neopterin to biopterin ratio (N/B)much higher than that of age-matched controls. The mean NIB in the parents of these patients was twice that of healthy unrelated adults. PTPS activity was measured in one of these patients with PTPS deficiency and in his family members; the patient was homozygous and his parents were heterozygous for PTPS deficiency. This result meant that N/Bcould be used as an index of PTPS activity. In healthy subjects studied cross-sectionally, urinary levels of pteridine decreased in groups of increasing age, and the same change was found in subjects with hyperphenylalaninemia studied cross-sectionally. Thus, pteridine values of patients can be compared meaningfully only with age-matched controls. The urinary N/Bis useful for the diagnosis of homozygotes and heterozygotes for PTPS deficiency.