New insights into iron homeostasis through the study of non-HFE hereditary haemochromatosis

• Published in: Best practice & research. Clinical haematology 2005-06, Vol.18 (2), p.235-250
• Main Authors: Roetto, Antonella, Camaschella, Clara
• Format: Article
• Language: English
• Subjects: Animals; Antimicrobial Cationic Peptides - genetics; Antimicrobial Cationic Peptides - metabolism; Cation Transport Proteins - genetics; Cation Transport Proteins - metabolism; ferroportin; GPI-Linked Proteins; haemochromatosis; Hemochromatosis - classification; Hemochromatosis - genetics; Hemochromatosis - metabolism; Hemochromatosis Protein; hemojuvelin; hepcidin; Hepcidins; HFE; Histocompatibility Antigens Class I - genetics; Homeostasis - physiology; Humans; iron; Iron - metabolism; Membrane Proteins - genetics; Membrane Proteins - metabolism; Mutation; Receptors, Transferrin - genetics; Receptors, Transferrin - metabolism; transferrin receptor 2
• ISSN: 1521-6926; 1532-1924
• DOI: 10.1016/j.beha.2004.09.004

Non- HFE haemochromatosis is a negative definition applied to all those haemochromatosis disorders that are unrelated to HFE mutations. Four genes are responsible for the distinct types of non- HFE haemochromatosis: hepcidin and hemojuvelin are the genes involved in type 2 or juvenile haemochromatosis, transferrin receptor 2 is involved in type 3 haemochromatosis, and ferroportin 1 is mutated in type 4, the atypical dominant form of primary iron overload. Molecular genetic studies of these conditions have greatly contributed to our understanding of the regulation of iron absorption. A milestone was the discovery that hepcidin, the key iron regulator in mice, is the gene mutated in the most severe, juvenile form of haemochromatosis. This finding indicates a fundamental role of hepcidin in inhibiting both iron absorption from duodenal cells and iron release from macrophages, and has opened up a new view of haemochromatosis as a disorder of hepcidin.