6-Pyruvoyltetrahydropterin Synthase Deficiency
6-pyruvoyl tetrahydropterin synthase (6-PTPS, 6-PTS, or PTS) catalyzes the elimination of inorganic triphosphate from dihydroneopterin triphosphate to form 6-pyruvoyltetrahydropterin. Thus, patients have elevated neopterin to biopterin ratios in urine and plasma. Reduced PTS activity can be documented in red blood cells. In the classic form of the disorder, patients have reduced catecholamine and serotonin metabolites, and an increased neopterin to biopterin level in CSF.
These patients are usually picked up on newborn screening as phenylketonurics, and show progressive signs of neurologic involvement in the first few months of life, including extrapyramidal signs, axial and truncal hypotonia, hypokinesia, feeding difficulties, choreoathetotic or dystonic limb movements, and autonomic symptoms.
Many of these patients, despite early diagnosis and supplementation with BH4 and neurotransmitter precursors, continue to manifest delays in development. A “peripheral” form of the disorder is characterized by normal central neurotransmitter levels, and less significant or transient hyperphenylalaninemia. Patients with the peripheral form have an excellent prognosis for normal neurologic development, provided the hyperphenylalaninemia is corrected by diet or BH4 administration.
