Intermittent Acute Porphyria — Demonstration of a Genetic Defect in Porphobilinogen Metabolism

Abstract In a family with intermittent acute porphyria (IAP) five affected members were found to have decreased erythrocyte uroporphyrinogen I (URO)-synthetase activity, when compared to unaffected relatives or normal controls. However, two seemingly unaffected siblings with normal urinary excretion of porphyrin precursors had low URO-synthetase activity. These siblings were given a single dose of δ-aminolevulinic acid (ALA) to mimic the endogenous overproduction of ALA that occurs in affected family members. The conversion of exogenous ALA to porphyrins excreted in urine and stool was decreased in these two siblings in a manner similar to the excretion pattern in patients with IAP. In one of these two siblings an acute attack of IAP developed spontaneously six months after completion of this study. By contrast, two siblings with normal erythrocyte URO-synthetase activity had normal conversion of ALA to porphyrins. These findings suggest that decreased URO-synthetase activity reflects the primary genetic ...