[Role of the hemochromatosis gene in prophyria cutanea tarda. Prospective study of 56 cases].Ann Dermatol Venereol. 2001 May; 128(5):600-4.AD
The cause of iron overload in prophyria cutanea tada is unknown. The aim of this work was to determine the frequency of the hemochromatosis gene (HFE) in 56 patients with porphyria cutanea tarda. We analyzed the relationship between HFE mutations and biochemical abnormalities in porphyria cutanea tarda and the interaction with other triggering factors of porphyria cutanea tarda (alcohol abuse, hepatitis C, drugs).
PATIENTS AND METHODS
Hepatitis C, alcohol abuse, drug intake and HFE mutations were determined in 56 patients with porphyria cutanea tarda (44 men and 12 women). Iron status was determined from transferrin saturation, serum iron, and serum ferritin. Liver metabolism was determined from liver chemistries: alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyl transpeptidase.
Thirty-nine patients (69.4 p. 100) carried HFE mutations, 18 (32.1 p. 100) were H63D heterozygous, 4 (7.1 p. 100) were H63D homozygous, 9 (16 p. 100) C282Y heterozygous, 8 (14.2 p. 100) compound C282Y/H63D heterozygous and none were C282Y homozygous. Comparison between porphyria cutanea tarda with and without mutations showed that compound C282Y/H63D heterozygous status 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 homozygous status was linked to iron overload but non-significantly: transferrin sturatin=0.53 vs 0.39 (p=0.06). The class with high iron overload (transferrin saturation > 0.45) was not linked with triggering factors of porphyria cutanea tarda. Hepatatic cytolysis was linked to alcohol abuse and hepatitis C but not to HFE mutations.
The frequencies of HFE mutations in Lyons France are halfway between Anglo-Saxon and Italian papers, highlighting the Celtic origin of C282Y mutation. Compound heterozygous and to a lesser degree H63D homozygous status explained the highest iron overload in our patients. This favors clinical expression of porphyria cutanea tarda. This iron overload due to HFE mutations is a new triggering factor of porphyria cutanea tarda independent of classical triggering factors: mutation of the erythrocytic uroporpyrinogen decarbocylase gene, alcohol abuse, hepatitis C, and drugs.