Genetic hemochromatosis: Pathophysiology, diagnostic and therapeutic management

P. Brissot (1, 2) , T. Cavey (1, 2) , M. Ropert (1, 2) , P. Guggenbuhl (1, 2) , Olivier Loréal (1)

1 Foie, métabolismes et cancer
2 CHU Pontchaillou [Rennes]

The term hemochromatosis (HC) corresponds to several diseases characterized by systemic iron overload of genetic origin and affecting both the quality of life and life expectancy. Major improvement in the knowledge of iron metabolism permits to divide these diseases into two main pathophysiological categories. For most HC forms (types 1, 2, 3 and 4B HC) iron overload is related to cellular hepcidin deprivation which causes an increase of plasma iron concentration and the appearance of plasma non-transferrin bound iron. In contrast, iron excess in type 4A ferroportin disease is related to decreased cellular iron export. Whatever the HC type, the diagnosis rests on a non-invasive strategy, combining clinical, biological and imaging data. The mainstay of the treatment remains venesection therapy with the perspective of hepcidin supplementation for hepcidin deprivation-related HC. Prevention of HC is critical at the family level and, for type 1 HC, remains a major goal, although still debated, at the population level.

Keywords: TFR2 gene; symptomatology; supplementation; SLC40A1 gene; Short Survey; sex difference; phlebotomy; pathophysiology; iron overload; iron chelation; hyperferritinemia; HFE2 gene; human; ferroportin; hepcidin; apheresis; cell transport; chromosome 1; chromosome 19; chromosome 2; chromosome 3; chromosome 7; disease classification; erythocytapheresis; gene; genetic screening; HAMP gene; hemochromatosis; HFE gene

Domains: Life Sciences [q-bio]; Human health and pathology; Endocrinology and metabolism

P. Brissot, T. Cavey, M. Ropert, P. Guggenbuhl, Olivier Loréal. Genetic hemochromatosis: Pathophysiology, diagnostic and therapeutic management. La Presse Médicale, 2017, 46 (12), pp.e288-e295. ⟨10.1016/j.lpm.2017.05.037⟩. ⟨hal-01671715⟩