Gene

Ferroportin

Biology

Hemochromatosis

Phlebotomy

Endocrinology

Mutation

Hereditary hemochromatosis

Computer science

Anemia

Genetics

Internal medicine

HAMP

Medicine

Hepcidin

Nature Reviews Disease Primers

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. Mutations in genes leading to hepcidin deficiency lead to haemochromatosis, a clinical syndrome characterized by dysregulated iron metabolism and cellular iron overload. This Primer by Brissot and colleagues discusses the aetiology, epidemiology and diagnosis of haemochromatosis and describes patient management and quality of life.

Haemochromatosis