Role in porphyria cutanea tarda of hemochromatosis gene (HFE): a prospective study of 56 cases

Background. The cause of iron overload in prophyria cutanea tada is unknown . The aim of this work was to determine the frequency of the hemochromatosi s gene (HFE) in 56 patients with porphyria cutanea tarda. We analyzed the r elationship between HFE mutations and biochemical abnormalities in porphyri a cutanea tarda and the interaction with other triggering factors of porphy ria cutanea tarda (alcohol abuse, hepatitis C, drugs). Patients and methods. Hepatitis C, alcohol abuse, drug intake and HFE mutat ions were determined in 56 patients with porphyria cutanea tarda (44 men an d 12 women). Iron status was determined from transferrin saturation, serum iron, and serum ferritin. Liver metabolism was determined from liver chemis tries: alanine aminotransferase, aspartate aminotransferase, and gamma-glut amyl transpeptidase. Results. Thirty-nine patients (69.4 p. 100) carried HFE mutations, 18 (32.1 p. 100) were H63D heterozygous, 4 (7.1 P too) were H63D homozygous, 9 (16 p. 100) C282Y heterozygous, 8 (14.2 p, loo) compound C282Y/H63D heterozygou s and none were C282Y homozygous. Comparison between porphyria cutanea tard a with and without mutations showed that compound C282Y/H63D heterozygous s tatus was significantly linked to iron overload: transferrin saturation = 0 .61 vs 0.39 (P = 0.0001) and serum iron = 32.9 vs 22.4 (p = 0.0046). H63D h omozygous status was linked to iron overload but nonsignificantly: transfer rin sturatin = 0.53 vs 0.39 (p = 0.06). The dass with high iron overload (t ransferrin saturation > 0.45) was not linked with triggering factors of por phyria cutanea tarda, Hepatatic cytolysis was linked to alcohol abuse and h epatitis C but not to HFE mutations. Discussion. The frequencies of HFE mutations in Lyons France are halfway be tween Anglo-Saxon and Italian papers, highlighting the Celtic origin of C28 2Y mutation. Compound heterozygous and to a lesser degree H63D homozygous s tatus explained the highest iron overload in our patients. This favors clin ical expression of porphyria cutanea tarda. This iron overload due to HFE m utations is a new triggering factor of porphyria cutanea tarda independent of classical triggering factors: mutation of the erythrocytic uroporpyrinog en decarbocylase gene, alcohol abuse, hepatitis C, and drugs.