Idiopathic hemochromatosis. Demonstration of recessive transmission and early detection by family HLA typing

N Engl J Med. 1977 Nov 10;297(19):1017-21. doi: 10.1056/NEJM197711102971901.


We studied iron overloading and HLA types in 24 sibships of patients with idiopathic hemochromatosis, of which 15 had at least two subjects with overt forms. HLA types of 84 unrelated patients were also investigated. Among siblings there was a significant association (P less than 0.0001) between the presence of hemochromatosis and the possession of the same two HLA haplotypes. The fact that overt forms of hemochromatosis depend on the presence of two specific homologous chromosomes strongly supports a recessive mode of transmission for the overt disease. The haplotypic equilibrium demonstrated in the unrelated patients group is another supporting argument. The lod-score value (2.239 for theta = 0.005) in six families available for study further supports the conclusion that a hemochromatosis gene is closely linked to the HLA-A locus. HLA typing in families with hemochromatosis could provide a means of early detection of subjects at risk before appearance of any sign of iron overload.

MeSH terms

  • Adult
  • Aged
  • Female
  • Genes, Recessive
  • Genetic Linkage
  • Genotype
  • HLA Antigens / analysis*
  • Hemochromatosis / diagnosis
  • Hemochromatosis / genetics*
  • Humans
  • Male


  • HLA Antigens