6-Pyruvoyl-Tetrahydropterin Synthase (PTPS) Deficiency

Persistent hyperphenylalaninemia may be caused by defects in metabolism or regeneration of tetrahydrobiopterin. 6-pyruvoyl-tetrahydropterin synthase (PTPS) deficiency is an inborn error of tetrahydrobiopterin (BH4) synthesis that accounts for approximately 60% of all tetrahydrobiopterin deficiencies. BH4 is a cofactor essential for phenylalanine hydroxylase, and tryptophan and tyrosine hydroxylases; decreased activities of the latter enzymes is likely the cause of the neurologic symptoms associated with this disorder. Infants develop neurological symptoms even though blood phenylalanine levels are normal. Approximately 80% of patients with PTPS deficiency present with the severe “typical” form characterized by early onset of severe neurological symptoms including microcephaly, psychomotor retardation, tonal abnormalities, seizures, hypothermia and hyperthermia (without infections), swallowing difficulties and hypersalivation. Other features include mental retardation and microcephaly. The clinical course of severe PTPS deficiency may be similar to that in other inborn errors of BH4 metabolism namely dihydropteridine reductase deficiency and GTP cyclohydrolase I deficiency. Less severely affected patients are classified as having a mild/peripheral or “atypical” form of PTPS deficiency with symptoms ranging from transient hyperphenylalanemia to cases where a mild form progresses into a severe form

Tests Available

Forms and Documents

Test Details

  • Confirmation of biochemical diagnosis
  • Carrier testing
  • Prenatal diagnosis in at risk pregnancies
  • Capillary Sequencing


4-5 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Buccal Swabs


  • 270.1 Phenylketonuria [PKU], Hyperphenylalaninemia
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