Hémochromatoses

Abstract

AbstractHemochromatoses benefit from a great clarification of their nosology thanks to the consideration of the mechanism underlying the development of iron overload. Thus, the mechanistic common denominator is hepcidin deficiency which, by stimulating the cellular iron export activity of ferroportin in the duodenum and the spleen, leads to a cascade: hyper-sideremia, appearance of non-transferrin bound iron that first targets the liver, and exerts cellular toxicity damaging key organs and corresponding to the development of hemochromatosis, that is source of morbidity and mortality. In the Caucasian subject, hemochromatosis linked to the HFE gene is by far the most frequent. Non HFE-related hemochromatoses are rare but multi-ethnic and often severe. The contribution of biology is major for the understanding of the pathophysiology (role of hypo-hepcidinemia), for the diagnosis (coefficient of transferrin saturation, ferritinemia) including the etiological identification (genetic tests), and for the therapeutic follow-up (importance of ferritinemia and possibly in the future of hepcidinemia). The diagnosis of hemochromatosis has become totally non-invasive (based on clinical, biological and imaging techniques) and its therapy, which remains based on phlebotomies, should in the future call for innovative approaches aimed at restoring normal iron metabolism.