DEVELOPMENT OF CHRONIC HEPATIC PORPHYRIA (PORPHYRIA-CUTANEA-TARDA) WITH INHERITED UROPORPHYRINOGEN DECARBOXYLASE DEFICIENCY UNDER EXPOSURE TO DIOXIN

Exposure to dioxin [2,3,7,8-tetrachlorodibenzo-p-dioxin] triggered a clinically manifest chronic hepatic porphyria (porphyria cutanea tarda) in 2 patients (brother and sister) with hereditary uroporphyrinogen decarboxylase deficiency. The patients showed a decrease of erythrocyte uroporphyrinogen decarboxylase activity to .apprx. 50% of controls even in reinvestigations after 3 yr; clinical symptoms and porphyrinuria had improved considerably. Only a subclinical phase of chronic hepatic porphyria persisted. Subnormal uroporphyrinogen decarboxylase activity could be determined in 9 family members. The remission of porphyria cutanea tarda into a subclinical phase occurred after chloroquine therapy. Subclinical phases of chronic hepatic porphyria (type A) in other family members remitted without special therapy. Among the 60 persons dioxin-exposed by the Seveso [Italy] accident, a secondary coproporphyrinuria was found in 22% of examined patients with transition to a subclinical chronic hepatic porphyria in 5 cases. The changes had subsided completely after 1 yr. A persistence of the transition state in 3 cases was probably due to alcohol influence. No case developed a porphyria cutanea tarda. The investigations showed that a hereditary disposition was necessary for biochemical and clinical expression of chronic hepatic porphyria after a unique dioxin exposure. This was not given in the sporadic cases: after a unique dioxin exposure they developed a symptomatic disturbance of porphyrin metabolism but not a clinically relevant chronic hepatic porphyria. A unique acute exposure to dioxin triggered the chronic hepatic porphyria disease process in persons with an underlying genetic abnormality of uroporphyrinogen decarboxylase.