Haemochromatosis and HFE gene

The discovery of the HFE gene has improved classification and diagnosis of iron overload. Most patients with a phenotypic diagnosis of haemochromatosis are bomozygote for the C282Y mutation. Among those with other genotypes, only compound heterozygotes, who present the C282Y mutation on one chromosome and the H63D on the other, may present with haemochromatosis, but with a low penetrance and a mild expression. Other patients usually present with another cause of iron overload, such as insulin resistance, alcoholic liver disease or liver cirrhosis. The practical management of haemochromatosis has been greatly modified, since liver biopsy is no more necessary for diagnosis in C282Y homozygotes, and is only needed for exclusion of cirrhosis. Family screening has also greatly benefited from genotyping. (Acta gastroelnterol. belg., 1999, 62, 403-409).