Hemochromatosis genes and other factors contributing to the pathogenesis of porphyria cutanea tarda

Inherited and acquired factors have been implicated in the pathogenesis of porphyria cutanea tarda (PCT), a disorder characterized by a photosensitive dermatosis and hepatic siderosis, This study, comprising 108 patients with PCT, was intended to define the role of hemochromatosis gene (HFE) mutatio ns in the expression of PCT and to determine the contribution of acquired f actors including alcohol, hepatitis C virus (HCV), and estrogen, The 2 know n HFE mutations, cysteine 282 tyrosine (Cys282Tyr) and histidine 63 asparag ine (His63Asp), were detected by polymerase chain reaction, and anti-HCV im munoglobulin G was detected serologically, Liver biopsies were graded for i ron content, inflammation, and fibrosis, Estimates of alcohol and estrogen use were based on a questionnaire, Of the PCT patients tested, 19% were hom ozygous for the Cys282Tyr mutation; controls were equal to 0.5%, The compou nd heterozygous genotype was detected in 7% of the POT patients; controls w ere less than 1%, The transferrin saturation, serum ferritin, and liver iro n burden of all PCT patients were higher than those of nonporphyric control s. The highest values were found in PCT patients homozygous for the Cys282T yr mutation. Of the patients studied, 59% were HCV positive (compared with 1.8% of the population), and 46% consumed more than 70 g of alcohol daily, Of the female patients, 63% were ingesting estrogens, Hepatic damage was mo st marked in patients with the Cys282Tyr/Cys282Tyr genotype who had HCV and drank heavily. Homozygosity for the Cys282Tyr mutation and HCV are the gre atest risk factors for expression of PCT, and in most patients, more than 1 risk factor was identified. It was common for patients with HCV to consume alcohol, Patients with PCT should be screened for HFE mutations and for HC V. (C) 2000 by The American Society of Hematology.