Erythrocyte uroporphyrinogen I synthase activity in diagnosis of acute intermittent porphyria.

Measurement of the activity of uroporphyrinogen I synthase provides an excellent laboratory aid in the diagnosis of acute intermittent porphyria, particularly in those patients who are asymptomatic or in whom the disease is not biochemically manifested by porphyrin precursor excretion. We describe here a simplified fluorometric method for measuring the activity of this enzyme in whole blood. The assay is based upon a coupled-enzyme procedure in which added delta-aminolevulinic acid and the dehydratase that is present in erythrocytes are used to generate porphobilinogen as substrate for uroporphyrinogen synthase. After appropriate incubation the protein is removed we sensitivity, specificity, and precision of the assay compare well with previously described procedures. Activity in nonporphyric male subjects was 31 (SD, 6.0) nmol of porphyrin formed per milliliter of erythrocytes per hour at 37 degrees C. Application of the method for identifying gene carriers of acute intermittent porphyria is demonstrated in three generations of an affected family.