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Histocompatibility antigens as markers of abnormal iron metabolism in idiopathic hemochromatosis.

To determine the frequency of HLA histocompatibility antigens in persons with idiopathic hemochromatosis and their usefulness as genetic markers of the disease, HLA typing for the A, B and C loci was carried out. HLA-A3 was found in 61% of 18 unrelated individuals with idiopathic hemochromatosis compared with 25% of 253 randomly chosen control subjects (P less than 0.001), and HLA-B7 was found in 50% and 22% respectively (P less than 0.025). Eighty-six members of seven families with idiopathic hemochromatosis were screened for abnormalities in iron metabolism with tests for serum iron concentration, transferrin saturation, serum ferritin concentration and iron content of the hepatocytes. Of the 14 persons selected for liver biopsy because of abnormalities detected by these tests, 8 had increased amounts of stainable iron in the hepatocytes. Body iron overload was subsequently demonstrated in six of the seven, who had undergone repeated phlebotomy. In sibships having one member with hemochromatosis, only 1 of 22 members had two haplotypes in common with the proband, whereas in sibships having more than 1 member with the disease 4 of 5 affected members had two haplotypes in common. HLA typing in families with hemochromatosis may provide a means of identifying persons at risk of acquiring the disease.