Hemochromatosis: genetics and pathophysiology

Annu Rev Med. 2006;57:331-47. doi: 10.1146/annurev.med.57.121304.131310.


A number of genetic disorders can result in the accumulation of excess iron in the body. These causes of hereditary hemochromatosis include defects in genes encoding HFE, transferrin receptor 2, ferroportin, hepcidin, and hemojuvelin. Hepcidin, with its cognate receptor, ferroportin, has emerged as a central regulator of iron homeostasis; all of the known causes of hemochromatosis appear to prevent this system from functioning normally. The most common form of primary hemochromatosis is that caused by C282Y mutation of the HFE gene. This mutation is most prevalent among Northern Europeans. Although the frequency of the homozygous genotype is approximately 5 per 1000, the disease itself is quite rare because the clinical penetrance of the genotype is very low.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antimicrobial Cationic Peptides / genetics
  • Cation Transport Proteins / genetics
  • GPI-Linked Proteins
  • Hemochromatosis / genetics*
  • Hemochromatosis / physiopathology*
  • Hemochromatosis Protein
  • Hepcidins
  • Histocompatibility Antigens Class I / genetics
  • Humans
  • Membrane Proteins / genetics
  • Penetrance
  • Receptors, Transferrin / genetics


  • Antimicrobial Cationic Peptides
  • Cation Transport Proteins
  • GPI-Linked Proteins
  • HAMP protein, human
  • HFE protein, human
  • HJV protein, human
  • Hemochromatosis Protein
  • Hepcidins
  • Histocompatibility Antigens Class I
  • Membrane Proteins
  • Receptors, Transferrin
  • TFR2 protein, human
  • metal transporting protein 1