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GTP cyclohydrolase I deficiency

Disease definition

GTP-cyclohydrolase I deficiency, an autosomal recessive genetic disorder, is one of the causes of malignant hyperphenylalaninemia due to tetrahydrobiopterin deficiency. Not only does tetrahydrobiopterin deficiency cause hyperphenylalaninemia, it is also responsible for defective neurotransmission of monoamines because of malfunctioning tyrosine and tryptophan hydroxylases, both tetrahydrobiopterin-dependent hydroxylases.

ORPHA:2102

Classification level: Subtype of disorder
  • Synonym(s):
    • GTPCH deficiency
    • Hyperphenylalaninemia due to GTP cyclohydrolase deficiency
  • Prevalence: <1 / 1 000 000
  • Inheritance: Autosomal recessive 
  • Age of onset: Infancy, Neonatal
  • ICD-10: E70.1
  • ICD-11: 5C59.01
  • OMIM: 233910
  • UMLS: C0268467
  • MeSH: C562656
  • GARD: 2844
  • MedDRA: -

Summary

Clinical description

When left untreated, the deficiency causes neurological signs at age 4 or 5 months, although clinical signs are often obvious from birth. The principal symptoms include: psychomotor retardation, tonicity disorders, convulsions, drowsiness, irritability, abnormal movements, hyperthermia, hypersalivation, and difficulty swallowing.

Diagnostic methods

GTP-cyclohydrolase I deficiency should be suspected in all infants with a positive neonatal screening test for phenylketonuria, especially when hyperphenylalaninemia is moderate. The most effective way to diagnose the disorder is to measure pteridine levels in urine and to confirm the result by measuring neurotransmitters (5-hydroxyindolacetic acid, homovanillic acid) in cerebrospinal fluid and with an oral tetrahydrobiopterin-loading test (20 mg/kg).

Management and treatment

The treatment attempts to bring phenylalaninemia levels back to normal (diet with restricted phenylalanine intake or prescription of tetrahydrobiopterin) and to restore normal monoaminergic neurotransmission by administering precursors (L-dopa/carbidopa and 5-hydroxytryptophane).

Expert reviewer(s):  Pr Jean-Louis DHONDT - Last update: February 2005

  A summary on this disease is available in Deutsch (2003) Español (2005) Français (2005) Italiano (2005) Nederlands (2005) Português (2005)

Detailed information

Guidelines

Disease review articles

ERN produced/endorsed by ERN(s)   FSMR produced/endorsed by FSMR(s)

Additional information

Further information on this disease

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The documents contained in this web site are presented for information purposes only. The material is in no way intended to replace professional medical care by a qualified specialist and should not be used as a basis for diagnosis or treatment.