Iron overload

Excess iron is toxic and may cause organ damage through generation of reactive oxygen species. Hereditary haemochromatosis is a primary iron overload due to mutations of genes that disrupt systemic iron homeostasis regulated by the hepcidin/ferroportin axis. The most frequent form is due to a recurrent mutation of HFE. Increased iron absorption leads to liver iron overload and risk of fibrosis, cirrhosis, hepatocellular carcinoma and other clinical complications. Treatment is based on regular phlebotomy that reverts body iron to normal. Secondary iron overload is caused by chronic blood transfusions, as in thalassaemia major or by excessive intestinal iron absorption induced by ineffective erythropoiesis, exemplified by non-transfusion-dependent-thalassaemia. Three compounds, desferrioxamine that is administered parenterally and the oral chelators deferiprone and deferasirox counteract iron excess when given either alone or in combination. Iron chelation may revert cardiomyopathy and significantly improve survival of thalassaemia major and of other chronically transfused patients.