Disease-related conditions in relatives of patients with hemochromatosis

N Engl J Med. 2000 Nov 23;343(21):1529-35. doi: 10.1056/NEJM200011233432104.


Background: Hemochromatosis occurs in approximately 5 white people per 1000 and is usually due to homozygosity for mutations in the HLA-linked HFE gene. Although screening has been proposed, the proportion of homozygotes with conditions related to hemochromatosis is uncertain.

Methods: We studied the prevalence of disease-related conditions among relatives of probands with hemochromatosis. We identified probands who presented to a clinic with signs or symptoms of hemochromatosis or who had elevated transferrin-saturation values. We identified homozygous relatives, mainly siblings, on the basis of HLA identity with the proband and by HFE genotyping. Disease-related conditions were cirrhosis, hepatic fibrosis, elevated amino-transferase values, and hemochromatotic arthropathy.

Results: We identified 214 homozygous relatives of 291 homozygous probands. Of the 113 men in this group (mean age, 41 years), 96 (85 percent) had iron overload, and 43 (38 percent) had at least one disease-related condition. Of the 52 men over 40 years of age, 27 (52 percent) had at least one disease-related condition. Of the 101 female homozygous relatives (mean age, 44 years), 69 (68 percent) had iron overload, and 10 (10 percent) had at least one disease-related condition. Of the 43 women over 50 years of age, 7 (16 percent) had at least one disease-related condition. If the proband had a disease-related condition, relatives who were men were more likely to have morbidity than if the proband had no disease-related condition.

Conclusions: A substantial number of homozygous relatives of patients with hemochromatosis--more commonly men than women--have conditions related to hemochromatosis that have yet to be detected clinically.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Family
  • Female
  • Hemochromatosis / classification
  • Hemochromatosis / complications*
  • Hemochromatosis / genetics*
  • Homozygote
  • Humans
  • Iron Overload / diagnosis
  • Iron Overload / etiology*
  • Liver Cirrhosis / diagnosis
  • Liver Cirrhosis / etiology
  • Liver Cirrhosis / genetics
  • Male
  • Middle Aged
  • Prevalence
  • Transaminases / blood
  • Transferrin / analysis


  • Transferrin
  • Transaminases