Disease Information for Tetrahydrobiopterin deficiency/Atypical PKU: Definition

Tetrahydrobiopterin Deficiency; Atypical Hyperphenylalaninemia;Atypical PKU; BH4 Deficiency

Malignant Hyperphenylalaninemia; Malignant PKU

Tetrahydrobiopterin Regeneration; Tetrahydrobiopterin Synthesis; tetrahydrobiopterin Deficiency is a rare genetic, neurological disorder present at birth; It is caused by an inherited inborn error of metabolism; Tetrahydrobiopterin is a natural substance (coenzyme) that enhances the action of other enzymes; When Tetrahydrobiopterin is deficient, an abnormally high blood level of the amino acid phenylalanine, along with low levels of certain neurotransmitters, usually occurs; To avoid irreversible neurological damage, diagnosis and treatment of this progressive disorder is essential as early as possible in life; The subdivisions of Tetrahydrobiopterin Deficiency are as follows:

Tetrahydrobiopterin Synthesis, GTP Cyclohydrolase I (GTPCH) Deficiency, 6-Pyruvoyl Tetrahydropterin Synthase (PTPS) Deficiency, Tetrahydrobiopterin Regeneration,

Pterin-4-alpha-Carbinolamine Dehydratase (PCD) Deficiency

Dihydropteridine Reductase (DHPR) Deficiency

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GTP cyclohydrolase I deficiency; GTPCH deficiency;

Hyperphenylalaninemia due to GTP cyclohydrolase deficiency; 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; 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); 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; 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); *Author : Prof J.L. Dhondt (February 2005)*-------[Orphanet website 2006]------------------------------

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