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Differential diagnosis of tetrahydrobiopterin deficiency
Author(s) -
Niederwieser A.,
Ponzone A.,
Curtius H. Ch.
Publication year - 1985
Publication title -
journal of inherited metabolic disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 102
eISSN - 1573-2665
pISSN - 0141-8955
DOI - 10.1007/bf01800657
Subject(s) - tetrahydrobiopterin , biopterin , homovanillic acid , phenylalanine , hyperphenylalaninemia , medicine , phenylalanine hydroxylase , tyrosine , endocrinology , enzyme , cerebrospinal fluid , biochemistry , chemistry , cofactor , amino acid , receptor , serotonin
Six hundred and seventy‐three children (483 newborns and 190 older selected children) were screened for tetrahydrobiopterin (BH 4 ) deficiency by HPLC of urine pterins and BH 4 load test. One patient with GTP cyclohydrolase I deficiency, 36 patients with dihydrobiopterin synthetase (DHBS) deficiency (of which six were in the newborn and 30 in the older children) and 14 with dihydropteridine reductase deficiency (DHPR) were found. All 37 patients with defective BH 4 biosynthesis responded to a BH 4 load by lowering of the elevated serum phenylalanine concentration but four of 14 patients with DHPR deficiency did not. Measurement of DHPR activity in blood spots on Guthrie cards is recommended. Since subvariants of patients with BH 4 deficiency exist, homovanillic acid, 5‐hydroxyindole acetic acid, pterins, phenylalanine, and tyrosine in cerebrospinal fluid should be measured for diagnosis and the control of therapy. The activity of the phosphate‐eliminating enzyme (a key enzyme in BH 4 biosynthesis and part of “DHBS”) was measured in human liver and activities of approx. 1 n U (mg protein) −1 were found. In the liver biopsy of a patient with DHBS deficiency no activity (less than 3% of controls) was demonstrated.