Uroporphyrinogen Decarboxylase (Uro-D) Defect in Erythrocytes in Chronic Hepatic Porphyrias

Abstract

The accumulation of porphyrins in liver tissue and the profile of porphyrins excreted in the urine, both characteristic for chronic hepatic porphyrias, strongly indicate that the primary defect in this disease complex involves uro-D (2). Recent research on the biochemical pathogenesis of chronic hepatic porphyrias using enzymatic studies in liver biopsy tissue have shown that uro-D is defective in all stages of chronic hepatic porphyrias (8). The primary enzymatic defect causes uro- and heptacarboxyporphyrin to accumulate in the liver; they are subsequently excreted in large amounts in the urine (2). Although alcohol or estrogens often trigger chronic hepatic porphyrias, it seemed probable that genetically fixed enzyme defects are responsible for the development of disturbances’ in hepatic porphyrin synthesis in the presence of chronic liver damage, since only about 5% of the patients with hepatic cirrhosis ever develop chronic hepatic porphyrias (7). In some patients with porphyria cutanea tarda (PCT) a diminished activity of uro-D in the erythrocytes was proved. This applies to sporadic cases (4, 6, 10), especially tumor patients with PCT as well as families with PCT (9). The findings of a diminished activity of uro-D in PCT did not remain unchallenged (1). Recent laboratory tests showed that the activity of uro-D in erythrocytes is equally reduced, not only in the majority of patients with chronic hepatic porphyrias, including PCT without proven family occurrence, but also in PCT patients with established family occurrence of the disease (11, 12).