Idiopathic hemochromatosis: a study of biochemical expression in 247 heterozygous members of 63 families: evidence for a single major HLA-linked gene

Abstract

The hypothesis has been advanced that the two genes on chromosome 6 determining idiopathic hemochromatosis are not identical alleles and therefore that the disease is not recessively inherited, but rather that two different genes are involved. A study of 63 families points to: (a) the rarity with which a single hemochromatosis gene finds biochemical expression (in only 1 of 5 cases), as revealed through determinations of serum iron, serum ferritin and the desferrioxamine test; (b) no difference in HLA-antigen marking between genes with and those without biochemical expression: (c) no difference other than that produced by chance in the biochemical expression of the two genes in families; and (d) the finding in one highly informative family of identical expression of the two genes. It is concluded that idiopathic hemochromatosis is determined by two homologous alleles in accordance with the classical mode of recessive inheritance.