[Measurement of dihydropteridine reductase activity in dried blood eluates: physiological and pathological...

Tetrahydrobiopterin deficiency in hyperphenylalaninemic babies has to be rapidly recognized since the disease requires a specific treatment. Although the measurement of pteridines in urine can detect most of tetrahydrobiopterin deficiencies, DHPR measurement has to be performed to circumvent the risk of missing DHPR deficiency, especially at the neonatal period. The possibility to measure DHPR activity in dried blood samples justifies itself by its convenience and simplicity. Expression of activity per mg of hemoglobin improves the precision of the assay by removing variation in the elution step (insufficient blood being loaded onto the filter paper, hematocrit variation, thickness of filter paper used). The distribution of DHPR activities, corrected from the progressive decrease with age, showed that 2.5% of the hyperphenylalaninemic or normal population have low levels of activity (below 50% of normal). This observation suggests that genetic variations may exist, as illustrated by the analysis of 11 families. Although blood DHPR measurement seems efficient for screening DHPR deficiency, the finding in a family of clinically normal subjects with zero activity illustrates the risk of false positive results of the enzymatic test.