title: Development of chronic hepatic porphyria (porphyria cutanea tarda) with inherited uroporphyrinogen decarboxylase deficiency under exposure to dioxin.
abstract: Exposure to dioxin triggered a clinically manifest chronic hepatic porphyria (porphyria cutanea tarda) in two patients (brother and sister) with hereditary uroporphyrinogen decarboxylase deficiency. The patients showed a decrease of erythrocyte uroporphyrinogen decarboxylase activity to approximately 50% of controls even in reinvestigations after three years, whereas clinical symptoms and porphyrinuria had improved considerably. Only a subclinical phase of chronic hepatic porphyria persisted. Subnormal uroporphyrinogen decarboxylase activity could be determined in altogether nine 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 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 one year. A persistence of the transition state in 3 cases is probably due to alcohol influence. None of these cases developed a porphyria cutanea tarda. The investigations showed that a hereditary disposition is necessary for biochemical and clinical expression of chronic hepatic porphyria after a unique dioxin exposure. This is not given in the sporadic cases: after a unique dioxin exposure they indeed develop a symptomatic disturbance of porphyrin metabolism but not a clinically relevant chronic hepatic porphyria. We conclude that a unique acute exposure to dioxin can trigger the chronic hepatic porphyria disease process in persons with an underlying genetic abnormality of uroporphyrinogen decarboxylase.
mesh_terms: D000328:Adult; D002262:Carboxy-Lyases / Q000172:deficiency*; D002908:Chronic Disease; D004147:Dioxins / Q000506:poisoning*; D005260:Female; D006801:Humans; D008107:Liver Diseases / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D009784:Occupational Diseases / Q000139:chemically induced*; D000072317:Polychlorinated Dibenzodioxins / Q000506:poisoning*; D011164:Porphyrias / Q000209:etiology*; D011166:Porphyrins / Q000652:urine; D014575:Uroporphyrinogen Decarboxylase / Q000172:deficiency*
chemical_list: D004147:Dioxins; D000072317:Polychlorinated Dibenzodioxins; D011166:Porphyrins; D002262:Carboxy-Lyases; D014575:Uroporphyrinogen Decarboxylase