Hemochromatosis: Inheritance of hemochromatosis: family studies

Introduction Hemochromatosis is an inherited disorder of iron metabolism characterized by excessive iron absorption that leads to parenchymal iron overload and eventually to organ damage. For nearly half a century, hemochromatosis was recognized as a separate disease entity before it was suggested by Sheldon that it could be an inborn error of metabolism. For many years the disease was named idiopathic or primary hemochromatosis, but over time evidence for the hereditability of hemochromatosis became compelling. The discovery by Simon in the 1970s that hemochromatosis was closely associated to certain human leukocyte antigens (HLA), i.e., HLA-A and HLA-B, is persuasive evidence of its hereditability. Subsequent epidemiologic surveys showed that hemochromatosis is one of the most common heritable disorders, with a prevalence of homozygosity of approximately 0.5% and a prevalence of heterozygosity of 10–15%. The high prevalence makes homozygote-heterozygote matings common, and thus a pseudodominant mode of inheritance. The discovery of specific molecular genetic markers for hemochromatosis has had a profound influence on understanding of this disorder. It will enable us to perform valid screening of the populations and to identify reliably persons at risk in affected families, and to obtain data on the expression and penetrance of the gene(s) in homozygous and heterozygous individuals.