Differential diagnosis of tetrahydrobiopterin deficiency

Abstract

Six hundred and seventy-three children (483 newborns and 190 older selected children) were screened for tetrahydrobiopterin (BH₄) deficiency by HPLC of urine pterins and BH₄ 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 BH₄ biosynthesis responded to a BH₄ 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 BH₄ 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 BH₄ 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.