Introduction: Hereditary hemochromatosis is a fairly common disease in the Caucasian population, with a prevalence estimated at between 1.5 to 3/1,000 inhabitants. Over the past few years, its symptomatology has altered; at present, its clinical aspect with diabetes mellitus, cirrhosis, and darker skin pigmentation only constitutes 10% of new cases of this disease.
Current knowledge and key points: In 1996, the discovery of the C282Y mutation in the HFE gene radically altered the diagnostic approach to hereditary hemochromatosis. At present, any patient admitted with an isolated case of asthenia, or with arthralgia or hypertransaminasemia should be examined via transferrin-saturation testing: if the transferrin saturation coefficient is > 45%, then the presence of the C282Y mutation should be investigated to confirm the diagnosis of hemochromatosis. A liver biopsy is no longer necessary to establish the diagnosis, but this is still useful in cases of possible cirrhosis, which is the main risk factor for hepatocellular carcinoma. Phlebotomy remains the sole recommended treatment, and should be undertaken in a case-specific manner. Family screening should be carried out for all first-degree relatives for every new case that is diagnosed.
Future prospects and projects: The discovery of the HFE gene has permitted hereditary hemochromatosis to be easily differentiated from other forms of hepatic iron overload including a new syndrome, dysmotabolic hepatosiderosis. Casos of homozygotic C282Y without hepatic iron overload have been described, but the clinical outcome of some of these cases requires further study, and adds to the controversy on whether systematic population screening should be made available.