TETRAHYDROBIOPTERIN AND QUINONOID DIHYDROBIOPTERIN CONCENTRATIONS IN CSF FROM PATIENTS WITH DIHYDROPTERIDINE REDUCTASE DEFICIENCY

Tetrahydrobiopterin (BH4) is the cofactor required for the tyrosine and tryptophan hydroxylases, these being the rate-limiting enzymes in the synthesis of dopamine and serotonin. During the reactions, BH4 is converted to quinonoid dihydrobiopterin (qBH2), which is reduced back to BH4 by the enzyme dihydropteridine reductase (DHPR). The turnover of dopamine and serotonin is low in DHPR deficiency (McKusick 261630) (Butler et al 1978) and it has been assumed that this is due to a lack of BH4. We have reported normal CSF BH4 levels in DHPR deficiency (Howells et al 1986); however, the method used to determine the concentration of BH4 in fact measured the total of [BH4 + qBH2], hence it is possible that some of the 'BH4' measured was in fact present as qBH2. It is important to establish whether normal levels of BH4 are present as, if this is the case, another explanation must be found for the reduced turnover of serotonin and dopamine. To resolve this issue, we determined the amount of qBH2 and BH4 in 7 CSFs from DHPR deficient patients and in 14 control CSFs using methodology that can distinguish between these two pterins (Heales and Hyland 1989). In addition we compared the total [BH4 + qBH2] in 31 samples of CSF from DHPR-deficient patients with an age-related reference population.