Hepcidin is decreased in TFR2 hemochromatosis

Blood. 2005 Feb 15;105(4):1803-6. doi: 10.1182/blood-2004-08-3042. Epub 2004 Oct 14.

Abstract

The hepatic peptide hepcidin is the key regulator of iron metabolism in mammals. Recent evidence indicates that certain forms of hereditary hemochromatosis are caused by hepcidin deficiency. Juvenile hemochromatosis is associated with hepcidin or hemojuvelin mutations, and these patients have low or absent urinary hepcidin. Patients with C282Y HFE hemochromatosis also have inappropriately low hepcidin levels for the degree of iron loading. The relationship between the hemochromatosis due to transferrin receptor 2 (TFR2) mutations and hepcidin was unknown. We measured urinary hepcidin levels in 10 patients homozygous for TFR2 mutations, all with increased transferrin saturation. Urinary hepcidin was low or undetectable in 8 of 10 cases irrespective of the previous phlebotomy treatments. The only 2 cases with normal hepcidin values had concomitant inflammatory conditions. Our data indicate that TFR2 is a modulator of hepcidin production in response to iron.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antimicrobial Cationic Peptides / deficiency*
  • Antimicrobial Cationic Peptides / urine*
  • Child, Preschool
  • Female
  • Hemochromatosis / genetics*
  • Hemochromatosis / urine*
  • Hepcidins
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • Receptors, Transferrin / genetics*
  • Receptors, Transferrin / physiology

Substances

  • Antimicrobial Cationic Peptides
  • HAMP protein, human
  • Hepcidins
  • Receptors, Transferrin
  • TFR2 protein, human