Background & aims: Two mutations have been described in the HFE gene: C282Y and H63D. The aim of this study was to determine the phenotype of the different HFE genotypes.
Methods: Clinical symptoms and iron data were examined according to HFE genotypes in 531 unrelated patients with unexplained liver iron overload and 579 relatives of hemochromatotic patients.
Results: Non-C282Y +/+ patients did not markedly differ in terms of iron overload or clinical expression according to genotype, except for compound heterozygotes, who had slightly increased transferrin saturation. This contrasted with the strikingly increased expression in C282Y homozygotes. Similar phenotype/genotype correlations were observed in relatives based on serum iron test results. Family transmission of iron overload linked to HFE was exceptional in non-C282Y +/+ siblings and frequent in C282Y homozygotes.
Conclusions: Iron overload in patients with the non-C282Y +/+ genotype is mild to moderate, strikingly lower than in C282Y homozygotes, and is not influenced by HFE genotype, except, to a small extent, for compound heterozygotes. The role of H63D mutation therefore seems to be marginal.