Document Detail

GTP cyclohydrolase I deficiency, a new enzyme defect causing hyperphenylalaninemia with neopterin, biopterin, dopamine, and serotonin deficiencies and muscular hypotonia.
MedLine Citation:
PMID:  6734669     Owner:  NLM     Status:  MEDLINE    
A 4-year-old patient is described with hyperphenylalaninemia, severe retardation in development, severe muscular hypotonia of the trunk and hypertonia of the extremities, convulsions, and frequent episodes of hyperthermia without infections. Urinary excretion of neopterin, biopterin, pterin, isoxanthopterin, dopamine, and serotonin was very low, although the relative proportions of pterins were normal. In lumbar cerebrospinal fluid, homovanillic acid, 5-hydroxyindoleacetic acid, neopterin and biopterin were low. Oral administration of L-erythro tetrahydrobiopterin normalized the elevated serum phenylalanine within 4 h, serum tyrosine was increased briefly and serum alanine and glutamic acid for a longer time. Urinary dopamine and serotonin excretion were also increased. Administration of an equivalent dose of D-erythro tetrahydroneopterin was ineffective and demonstrated that this compound is not a cofactor in vivo and cannot be transformed into an active cofactor. GTP cyclohydrolase I activity was not detectable in liver biopsies from the patient. The presence of an endogenous inhibitor in the patient's liver was excluded. This is the first case of a new variant of hyperphenylalaninemia in which the formation of dihydroneopterin triphosphate and its pterin metabolites in liver is markedly diminished. Normal activities of xanthine oxidase and sulfite oxidase were apparent since uric acid levels were normal and no increase in hypoxanthine, xanthine, and S-sulfocysteine concentrations could be observed in urine. It is concluded that the molybdenum cofactor of these enzymes may not be derived from dihydroneopterin triphosphate in man. Also, since no gross abnormalities in the patient's immune system could be found, it seems unlikely that dihydroneopterin triphosphate metabolites, such as neopterin, participate actively in immunological processes, as postulated by others. See Note added in proof.
A Niederwieser; N Blau; M Wang; P Joller; M Atarés; J Cardesa-Garcia
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Publication Detail:
Type:  Case Reports; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  European journal of pediatrics     Volume:  141     ISSN:  0340-6199     ISO Abbreviation:  Eur. J. Pediatr.     Publication Date:  1984 Feb 
Date Detail:
Created Date:  1984-08-02     Completed Date:  1984-08-02     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7603873     Medline TA:  Eur J Pediatr     Country:  GERMANY, WEST    
Other Details:
Languages:  eng     Pagination:  208-14     Citation Subset:  IM    
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MeSH Terms
Aminohydrolases / deficiency*
Biopterin / analogs & derivatives,  biosynthesis*,  deficiency,  therapeutic use
Child, Preschool
Dopamine / deficiency
GTP Cyclohydrolase / deficiency*
Liver / enzymology
Metabolism, Inborn Errors / complications*,  drug therapy,  metabolism
Muscle Hypotonia / etiology
Phenylalanine / blood*
Pteridines / biosynthesis*
Serotonin / deficiency
Reg. No./Substance:
0/Pteridines; 17528-72-2/5,6,7,8-tetrahydrobiopterin; 22150-76-1/Biopterin; 50-67-9/Serotonin; 63-91-2/Phenylalanine; 670-65-5/Neopterin; EC 3.5.4.-/Aminohydrolases; EC Cyclohydrolase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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