A time course of hepcidin response to iron challenge in patients with HFE and TFR2 hemochromatosis

Haematologica. 2011 Apr;96(4):500-6. doi: 10.3324/haematol.2010.033449. Epub 2010 Dec 20.


Background: Inadequate hepcidin production leads to iron overload in nearly all types of hemochromatosis. We explored the acute response of hepcidin to iron challenge in 25 patients with HFE-hemochromatosis, in two with TFR2-hemochromatosis and in 13 controls. Sixteen patients (10 C282Y/C282Y homozygotes, 6 C282Y/H63D compound heterozygotes) had increased iron stores, while nine (6 C282Y/C282Y homozygotes, 3 C282Y/H63D compound heterozygotes) were studied after phlebotomy-induced normalization of iron stores.

Design and methods: We analyzed serum iron, transferrin saturation, and serum hepcidin by both enzyme-linked immunosorbent assay and mass-spectrometry at baseline, and 4, 8, 12 and 24 hours after a single 65-mg dose of oral iron.

Results: Serum iron and transferrin saturation significantly increased at 4 hours and returned to baseline values at 8-12 hours in all groups, except in the iron-normalized patients who showed the highest and longest increase of both parameters. The level of hepcidin increased significantly at 4 hours and returned to baseline at 24 hours in controls and in the C282Y/H63D compound heterozygotes at diagnosis. The hepcidin response was smaller in C282Y-homozygotes than in controls, barely detectable in the patients with iron-depleted HFE-hemochromatosis and absent in those with TFR2-hemochromatosis. Conclusions Our results are consistent with a scenario in which TFR2 plays a prominent and HFE a contributory role in the hepcidin response to a dose of oral iron. In iron-normalized patients with HFE hemochromatosis, both the low baseline hepcidin level and the weak response to iron contribute to hyperabsorption of iron.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antimicrobial Cationic Peptides / blood*
  • Ferritins / blood
  • Genotype
  • Hemochromatosis / blood*
  • Hemochromatosis / genetics*
  • Hemochromatosis Protein
  • Hepcidins
  • Histocompatibility Antigens Class I / genetics
  • Humans
  • Iron / administration & dosage*
  • Iron / blood*
  • Iron / metabolism
  • Male
  • Membrane Proteins / genetics
  • Middle Aged
  • Receptors, Transferrin / genetics
  • Time Factors


  • Antimicrobial Cationic Peptides
  • HAMP protein, human
  • HFE protein, human
  • Hemochromatosis Protein
  • Hepcidins
  • Histocompatibility Antigens Class I
  • Membrane Proteins
  • Receptors, Transferrin
  • TFR2 protein, human
  • Ferritins
  • Iron