Hereditary iron overload: update on pathophysiology, diagnosis, and treatment

Am J Hematol. 2006 Mar;81(3):202-9. doi: 10.1002/ajh.20493.


Hereditary hemochromatosis, a very common genetic defect in the Caucasian population, is characterized by progressive tissue iron overload which leads to irreversible organ damage if it is not treated timely. The elucidation of the molecular pathways of iron transport through cells and its control has led to the understanding of various genetic iron-loading conditions. Four types of inherited iron overload have been recognized: type 1, the most common form with an autosomal recessive inheritance, is associated with mutations in the HFE gene on chromosome 6; type 2 (juvenile hemochromatosis) is an autosomal recessive disorder with causative mutations identified in the HJV gene (subtype A) on chromosome 1 and the HAMP gene (subtype B) on chromosome 19; type 3 has also an autosomal recessive inheritance with mutations in the TfR2 gene on chromosome 3; type 4 is an autosomal dominant condition with heterozygous mutations in the ferroportin 1 gene on chromosome 2. In this review, the genetics, pathophysiology, diagnosis, clinical features, and management of these different types of hereditary hemochromatosis are briefly discussed.

Publication types

  • Review

MeSH terms

  • Antimicrobial Cationic Peptides / genetics
  • Antimicrobial Cationic Peptides / metabolism
  • Cation Transport Proteins / genetics
  • Cation Transport Proteins / metabolism
  • Chromosomes, Human / genetics
  • Chromosomes, Human / metabolism
  • Genes, Dominant / genetics
  • Genes, Recessive / genetics
  • Hemochromatosis / classification
  • Hemochromatosis / diagnosis*
  • Hemochromatosis / genetics
  • Hemochromatosis / metabolism*
  • Hemochromatosis / therapy*
  • Hemochromatosis Protein
  • Hepcidins
  • Heterozygote
  • Histocompatibility Antigens Class I / genetics
  • Histocompatibility Antigens Class I / metabolism
  • Humans
  • Iron / metabolism
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Receptors, Transferrin / genetics
  • Receptors, Transferrin / metabolism


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