HEREDITARY HEMOCHROMATOSIS - PHENOTYPIC-EXPRESSION OF THE DISEASE

Previous studies have shown that hemochromatosis is an inherited, autosomal-recessive disease and that the gene is closely linked to the HLA locus on chromosome 6. We obtained a lod score for linkage of +9.8 for a recombination fraction of 0.0 and a gene frequency of 0.056, the frequency estimated in this population. We studied the phenotypic expression of the disease in 261 members of 10 pedigrees. In heterozygotes over 20 years of age, there was an intermediate increase in transferrin saturation and a limited increase in hepatic iron but no clinical manifestations. In male heterozygotes, the average amount of iron in the liver increased from about 0.2 to 1.3 g. Abnormal homozygotes accumulated iron progressively with time, with men accumulating about 18 g in the liver. All measurements of iron status were increased in abnormal homozygotes. Hemochromatosis is inherited as an autosomal-recessive disease, with partial biochemical expression in heterozygotes. (N Engl J Med 301:175–179, 1979) EXISTING evidence indicates that hemochromatosis is an autosomal-recessive disorder and that the locus for hemochromatosis is closely linked to the HLA region on chromosome 6.1,2 Simon et al.1 obtained a lod score of +2.2 for linkage to the HLA region. We used likelihood analysis to compare a dominant model with a recessive model without linkage to the HLA locus.2 The dominant model was rejected. We obtained a lod score of +5.6 for linkage between the HLA locus and the hemochromatosis locus in a recessive model with partial biochemical expression in heterozygotes. A lod score indicates the relative certainty with which. © 1979, Massachusetts Medical Society. All rights reserved.