Disease-related conditions in relatives of patients with hemochromatosis.

Background: Hemochromatosis occurs in approximately 5 white people per 1000 and is usually due to homozygosity for mutations in the HLA-linked HFE gen e. 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 rela tives of probands with hemochromatosis. We identified probands who presente d 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 genotypi ng. Disease-related conditions were cirrhosis, hepatic fibrosis, elevated a minotransferase 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 iro n 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 disea se-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. (N Engl J Med 200 0;343:1529-35.) (C) 2000, Massachusetts Medical Society.