Porphyria cutanea tarda (PCT) is caused by a decreased activity of the hepatic enzyme uroporphyrinogen decarboxylase (URO-D). This deficiency causes overproduction, hepatic deposition, and increased excretion of uroporphyrin. Iron overload and hepatic viral infections are considered aggravating factors of the disease. Two forms of PCT have been described, as follows: a familial one with an inherited decrease of URO-D activity in all tissues and a sporadic one with a decreased activity of URO-D restricted to the liver. To assess whether the hepatic URO-D returns to normal during a remission of the disease, this activity was measured in liver biopsy samples in 24 sporadic PCT patients. The hepatic and urinary porphyrin concentrations were also measured. Viral status and histopathological findings were analyzed to assess their involvement in PCT. Six patients treated by phlebotomy to reduce hepatic iron and who were considered to be in clinical remission, characterized by a disappearance of cutaneous lesions, showed higher hepatic URO-D activities and lower hepatic porphyrin concentrations than did patients with overt PCT. The medians of these variables, however, did not achieve normal values. The hepatic URO-D activity showed a significant inverse relationship with both hepatic porphyrins and urinary uroporphyrin excretion. Hepatic URO-D activity was not reduced by hepatitis C virus (HCV) infection and liver damage. We conclude that the achievement of remission in PCT largely depends on the transient normalization of hepatic URO-D activity. A small increase in hepatic coproporphyrin in nonporphyric patients could reflect hepatic injury/iron/alcohol-induced oxidative stress oxidizing the accumulated heme precursors rather than a direct effect on hepatic URO-D enzyme.

Key Clinical Message: Congenital dyserythropoietic anemias (CDAs) are displayed by ineffective erythropoiesis. The wide variety of phenotypes observed in CDA patients makes differential diagnosis difficult; identification of the genetic variants is crucial in clinical management. We report the fifth case of a patient with unclassified CDAs, after genetic study, with CDA type IV.