Porphyria cutanea tarda, or the uroporphyrinogen decarboxylase deficiency diseases

Abstract

The term "porphyria cutanea tarda" originally described the dermatological manifestations of various chronic porphyrias. Its usage now is usually restricted to disorders associated with a deficiency of uroporphyrinogen decarboxylase (UROD), for which the term "UROD-deficiency" may be more appropriate. Four etiologic agents have been implicated in this condition: alcohol, oral estrogens, halogenated aromatic hydrocarbons, and iron. An inherited deficiency of UROD is also recognized, with increased susceptibility to these agents. Certain halogenated aromatic hydrocarbons can cause UROD-deficiency in animals and synergism with iron is demonstrable in this model. Neither ethanol nor estrogen has been shown to cause UROD-deficiency in animals. Treatment by venesection to reduce total body iron is safe and effective. The 4-aminoquinoline antimalarial drugs also provide effective treatment, possibly by lysis of affected liver cells. Unlike venesection, they may not reverse the biochemical lesion which causes porphyrins to accumulate. The mechanism of acquired UROD-deficiency is not clear but animal studies suggest a role for the hepatic mixed function oxygenases which initiate iron-dependent inactivation of UROD. Diagnosis is simple, often requiring only appropriate clinical data and testing of a random urine sample. Although not common, the disorder is the most frequently diagnosed disturbance of porphyrin metabolism in many countries, and further insight into its unusual pathogenesis may clarify the hepatotoxic effects of the 4 etiologic agents.