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GTR Home > Conditions/Phenotypes > 6-Pyruvoyl-tetrahydrobiopterin synthase deficiency

6-Pyruvoyl-tetrahydrobiopterin synthase deficiency

Synonyms
6-Pyruvoyltetrahydropterin Synthase Deficiency; BH4-deficient hyperphenylalaninemia A; HYPERPHENYLALANINEMIA, TETRAHYDROBIOPTERIN-DEFICIENT, DUE TO PTS DEFICIENCY; Hyperphenylalanemia, BH4-deficient, A; Hyperphenylalaninemia due to 6-pyruvoyl-tetrahydropterin synthase deficiency; PTS DEFICIENCY
Modes of inheritance
Autosomal recessive inheritance (Orphanet)

Summary

Excerpted from the GeneReview: PTS-Related Tetrahydrobiopterin Deficiency (PTPSD)
PTS-related tetrahydrobiopterin deficiency (PTPSD) results in a lack of tetrahydropterin, an important cofactor for phenylalanine hydroxylase (PAH), tyrosine hydroxylase, and tryptophan hydroxylase. Deficiency can thus lead to neurotransmitter and neuropsychiatric disorders. The clinical spectrum of PTPSD is broad and differs according to age of onset, severity of disease, and whether preventative therapies were initiated and maintained from an early age. In the severe form, clinical symptoms may become apparent in the neonatal period and can include hypotonia, movement disorders, abnormal eye movements, autonomic dysregulation, and impaired development. Without treatment, developmental delays become more marked. Neurologic symptoms (dysarthria, dystonia, tremors, abnormal gait, parkinsonism, oculogyric crises, motor tics) may be ameliorated by treatment with sapropterin dihydrochloride and neurotransmitter precursors. Other features of the condition can include psychiatric comorbidities (ADHD, anxiety, depression), infant feeding difficulties leading to early growth failure, hyperprolactinemia, growth hormone deficiency, sleep issues, and autonomic dysfunction; many of these features can be ameliorated by appropriate treatment. In treated individuals, development often improves during adolescence, with many adults having a normal IQ level. In the mild (peripheral) form, affected individuals are usually asymptomatic apart from an increase in phenylalanine (Phe) levels. Some remain asymptomatic. However, with time, some have mild developmental delays and can develop deficiency of neurotransmitter production, such that treatment of some asymptomatic individuals may be required.
Full text of GeneReview (by section):
Summary
Diagnosis
Clinical Characteristics
Genetically Related (Allelic) Disorders
Differential Diagnosis
Management
Genetic Counseling
Resources
Molecular Genetics
Chapter Notes
References
Authors:
Thomas Opladen
Nicola Longo
Nenad Blau
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Available tests

49 tests are in the database for this condition.

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Clinical tests (49 available)

Biochemical Genetics Tests

Molecular Genetics Tests

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  • Also known as: PTPS, PTS
    Summary: 6-pyruvoyltetrahydropterin synthase

Clinical features

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Imported from Human Phenotype Ontology (HPO)

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Reviews

Clinical resources

Practice guidelines

  • ACMG ACT, 2022
    American College of Medical Genetics and Genomics, Newborn Screening ACT Sheet, Elevated Phenylalanine, Phenylalanine hydroxylase deficiency (PAH), 2022
  • ACMG Algorithm, 2022
    American College of Medical Genetics and Genomics, Algorithm, PAH deficiency: Elevated Phenylalanine, 2022

Molecular resources

Consumer resources

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