Recent years have witnessed tremendous advances in the fields of pathophysiology, diagnosis and management of hereditary hemochromatosis (HH) and other iron overload syndromes, the dreadful consequences of which are fully preventable by early diagnosis and treatment. Missense mutations in HFE, a newly discovered gene encoding for a major histocompatibility class-I like molecule, have been found to be strictly associated with most cases of HH. The mechanisms by which a dysfunctional HFE molecule determines increased absorption of iron in HH are on the way to be fully clarified, due to the availability of a knockout mouse model. Epidemiologic studies have shown that HH is one of the most common human hereditary disorders. The possibility to identify HFE heterozygotes by means of a simple genetic test have prompted studies on the association between HFE mutations and iron overload syndromes different from HH. In the era of the historic completion of the human genome projects, genetic testing for HH may soon qualify for being adopted in universal population screening policies. In the present paper, the recent advances in the fields of genetics and pathophysiology of HH and other iron overload syndromes will be summarized. Furthermore, its clinical features, pathology and treatment will be reviewed, and the emerging issues of cost-effective diagnosis and of possible population screening strategies will be succintly discussed.
