Abstract
Haemochromatosis is defined as systemic iron overload of genetic origin, caused by a reduction in the concentration of the iron regulatory hormone hepcidin, or a reduction in hepcidin–ferroportin binding. Hepcidin regulates the activity of ferroportin, which is the only identified cellular iron exporter. The most common form of haemochromatosis is due to homozygous mutations (specifically, the C282Y mutation) in HFE, which encodes hereditary haemochromatosis protein. Non-HFE forms of haemochromatosis due to mutations in HAMP, HJV or TFR2 are much rarer. Mutations in SLC40A1 (also known as FPN1; encoding ferroportin) that prevent hepcidin–ferroportin binding also cause haemochromatosis. Cellular iron excess in HFE and non-HFE forms of haemochromatosis is caused by increased concentrations of plasma iron, which can lead to the accumulation of iron in parenchymal cells, particularly hepatocytes, pancreatic cells and cardiomyocytes. Diagnosis is noninvasive and includes clinical examination, assessment of plasma iron parameters, imaging and genetic testing. The mainstay therapy is phlebotomy, although iron chelation can be used in some patients. Hepcidin supplementation might be an innovative future approach.
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Acknowledgements
B.d.G. has received a grant from Haemochromatosis Australia to conduct haemochromatosis research. C.E.M. was supported in part by grant 5R24 DK09984603 from the National Institute of Health and Digestive and Kidney Diseases. The authors thank B. Skikne (University of Kansas Medical Center) for his contributions to the section on Epidemiology.
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Introduction (P.B.); Epidemiology (C.E.M.); Mechanisms/pathophysiology (O.L.); Diagnosis, screening and prevention (P.B.); Management (P.C.A.); Quality of life (B.d.G.); Outlook (A.P.); overview of the Primer (P.B.).
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P.B. has received lecture fees from Novartis and consulting fees from Novartis and La Jolla Pharmaceutical Company. A.P. has received lecture fees from Novartis, and consulting fees from Novartis, La Jolla Pharmaceutical Company and Mitsubishi Tanabe Pharma Corporation. O.L. has received a research grant from Novartis. All other authors declare no competing interests.
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Brissot, P., Pietrangelo, A., Adams, P. et al. Haemochromatosis. Nat Rev Dis Primers 4, 18016 (2018). https://doi.org/10.1038/nrdp.2018.16
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DOI: https://doi.org/10.1038/nrdp.2018.16
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