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Haemochromatosis
journal contribution
posted on 2023-05-19, 17:05 authored by Brissot, P, Pietrangelo, A, Adams, PC, Barbara de GraaffBarbara de Graaff, McLaren, CE, Loreal, OHaemochromatosis 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.
History
Publication title
Nature Reviews. Disease PrimersVolume
4Article number
18016Number
18016Pagination
1-15ISSN
2056-676XDepartment/School
Menzies Institute for Medical ResearchPublisher
Nature Publishing GroupPlace of publication
United KingdomRights statement
Copyright 2018 Macmillan Publishers Limited, part of Springer NatureRepository Status
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