[Hereditary hemochromatosis]

Abstract

Hereditary hemochromatosis is an inherited disorder of iron metabolism in the Caucasian population with an autosomal recessive inheritance and a prevalence between 1 in 200 and 1 in 500. Until the discovery of HFE gene the diagnosis of hemochromatosis required documentation of iron overload or family linkage using HLA testing. The discovery of HFE gene has established the foundation for a better understanding of iron homeostasis and has changed hemochromatosis management: liver biopsy, gold standard diagnostic, was replaced by genetic test and it was suggested that population screening using genetic testing might be ideal for HFE related hemochromatosis. Considered for long time a unitary disease, a monogenic disorder characterized by excess tissue deposits of iron and subsequently organ damage, hemochromatosis is in fact a polygenic disease with many faces. The Online Mendelian Inheritance in Man database has lists four types of hereditary hemochromatosis, each of them caused by a different gene mutation (hepcidine, hemojuvelin, transferring receptor 2, ferroportin). The basic features shared by iron overload disorders associated with mutation in HFE, hepcidine, hemojuvelin, transferring receptor 2, ferroportin gene indicate that they are genetic variation of the same syndrome. Hereditary hemochromatosis must be distinguished from the other syndrome of iron overload and the classic term hereditary hemochromatosis should be reserved only for HFE related hemochromatosis.