C282Y and H63D mutation of the hemochromatosis gene in German porphyria cutanea tarda patients

Background and aims: Patients with porphyria cutanea tarda (PCT) have a sus ceptibility to reversible inactivation of hepatocyte uroporphyrinogen decar boxylase, which can be triggered by alcohol, hepatitis C virus, and other a gents. Inherited factors that may predispose to PCT include the C282Y mutat ion in the hemochromatosis (HFE) gene. Methods: We analyzed the hemochromat osis mutations C282Y and H63D in liver biopsies and serum samples of 190 Ge rman patients (mean age 48 +/- 12.5 years) with sporadic PCT. The hepatic i ron concentration was determined within the liver tissue. Age-matched healt hy blood donors (115 donors) served as controls. Results: The C282Y and H63 D mutations were found in 75 (39%) and 85 (45%) of 190 patients with PCT, r espectively. Twenty-two patients (12%) were homozygous for the C282Y mutati on, and eighteen patients (9%) were compound heterozygotes, displaying both the C282Y and the H63D mutation. Within the control group, 3 of 115 patien ts were heterozygous for C282Y (3%) and 12 for H63D (10%). Serum and hepati c iron, ferritin, transferrin saturation, or liver enzymes did not differ s ignificantly between patients with or without HFE mutations. Conclusions: T he high frequency of homo- and heterozygosity for the C282Y and H63D allele s strongly suggests that these mutations are important predisposing factors for PCT in German patients.