Genetic hemochromatosis is an
iron overload disease that is mainly related to the C282Y mutation in the HFE gene. This gene controls the expression of
hepcidin, a
peptide secreted in plasma by the liver and regulates systemic
iron distribution. Homozygous C282Y mutation induces
hepcidin deficiency, leading to increased circulating
transferrin saturation, and ultimately,
iron accumulation in organs such as the liver, pancreas, heart, and bone.
Iron in excess may induce or favor the development of complications such as
cirrhosis, liver cancer, diabetes,
heart failure,
hypogonadism, but also complaints such as
asthenia and disabling
arthritis.
Iron depletive treatment mainly consists of venesections that permit the removal of
iron contained in red blood cells and the subsequent mobilization of stored
iron in order to synthesize
hemoglobin for new erythrocytes. It is highly efficient in removing excess
iron and preventing most of the complications associated with excess
iron in the body. However, this treatment does not target the biological mechanisms involved in the
iron metabolism disturbance. New treatments based on the increase of
hepcidin levels, by using
hepcidin mimetics or inducers, or inhibitors of the
iron export activity of
ferroportin protein that is the target of
hepcidin, if devoid of significant secondary effects, should be useful to better control
iron parameters and symptoms, such as
arthritis.