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Clinical role of pteridine therapy in tetrahydrobiopterin deficiency
Author(s) -
Smith I.,
Hyland K.,
Kendall B.,
Leeming R.
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/bf01800658
Subject(s) - biopterin , tetrahydrobiopterin , pterin , pteridine , neopterin , phenylalanine hydroxylase , endocrinology , medicine , phenylalanine , hyperphenylalaninemia , chemistry , cerebrospinal fluid , folinic acid , pharmacology , biochemistry , enzyme , cofactor , chemotherapy , nitric oxide , amino acid , nitric oxide synthase , fluorouracil
In most patients with deficiency of tetrahydrobiopterin (BH 4 ) continuous administration of BH 4 or of a synthetic analogue such as 6‐methyltetrahydropterin (6‐MPH 4 ) lowers plasma phenylalanine concentrations to the therapeutic range. The effective dose of BH 4 varies from 1 to 2 mg kg −1 daily in patients with defective biopterin synthesis, to 5 mg kg −1 or more in patients with dihydropteridine reductase (DHPR) deficiency. The cost of 2 mg kg −1 day −1 of BH 4 is comparable to the cost of a low phenylalanine diet. Higher doses of pterins given orally (20 mg kg −1 ) raise the levels of tetrahydropterin in cerebrospinal fluid (CSF) to normal in patients with defective biopterin synthesis in whom initial concentration of biopterin species are low. In some, but not all, such patients pterin therapy also raises CSF amine metabolite concentrations and ameliorates symptoms. High dose therapy does not appear to be effective in raising CSF pterin levels in patients with DHPR deficiency who already accumulate dihydrobiopterin (BH 2 ) in CSF. Central folate deficiency is an additional cause of neurological deterioration in patients with DHPR deficiency who require supplementation with folate as folinic acid. It is suggested that the accumulation of BH 2 in such patients competitively interferes with folate metabolism.