Decreased activity of hepatic uroporphyrinogen decarboxylase in sporadic porphyria cutanea tarda.

To investigate the role of uroporphyrinogen decarboxylase in the pathogenesis of the sporadic form of porphyria cutanea tarda, we measured this enzyme in liver, erythrocytes and cultured skin fibroblasts, and also measured coproporphyrinogen oxidase and the total iron concentration in liver. The mean uroporphyrinogen decarboxylase activity was lower in liver from seven male patients (9.0 pmol of coproporphyrin per minute per milligram of protein) than in 12 controls, including seven with alcoholic liver disease (22.3 pmol per minute per milligram; P less than 0.05). Coproporphyrinogen oxidase activities were the same in each group. Liver iron concentrations were lower during remission, but uroporphyrinogen decarboxylase activities were not related to clinical activity for uroporphyrin excretion. Erythrocyte and fibroblast enzyme activities were the same as in normal subjects. A hepatic uroporphyrinogen decarboxylase defect is a prerequisite for the development of porphyria cutanea tarda, but other factors, which probably do not alter uroporphyrinogen decarboxylase activity, determine the clinical onset. In sporadic porphyria cutaneous tarda, the enzyme defect appears to be restricted to the liver.