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 (NIB) 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 NIB could be used as an index of PTPS activity. In healthy subjects studied crosssectionally, 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 IB is useful for the diagnosis of homozygotes and heterozygotes for PTPS deficiency.

Autosomal dominant guanosine triphosphate cyclohydrolase I deficiency (Segawa disease)

“…It is shown that the pteridine metabolism has a critical period beginning early in infancy and extending to early childhood 93. In addition, the D1‐direct pathways mature earlier, and the D2‐indirect pathways mature later 95, 96. Thus, the DA neuron in which the DA synthesis is modulated by pteridine metabolism might regulate DA receptors that mature early in the developmental course.…”

Molecular analysis and long-term follow-up of patients with different forms of 6-pyruvoyl-tetrahydropterin synthase deficiency

“…Reports about the long-term treatment and outcome of patients with BH 4 de®ciency are still scarce [2,44,47,49]. Many of the patients diagnosed late are retarded and some diagnosed in the ®rst weeks of life did not respond clinically to dierent treatment protocols.…”