Hereditary hemochromatosis (https://omim.org/entry/235200) is an autosomal recessive disorder of iron metabolism wherein the body accumulates excess iron (summary by Feder et al., 1996). Excess iron is deposited in a variety of organs leading to their failure, and resulting in serious illnesses including cirrhosis, hepatomas, diabetes, cardiomyopathy, arthritis, and hypogonadotropic hypogonadism. Severe effects of the disease usually do not appear until after decades of progressive iron loading. Removal of excess iron by therapeutic phlebotomy decreases morbidity and mortality if instituted early in the course of the disease. Classic hemochromatosis (HFE) is most often caused by mutation in a gene designated HFE on chromosome 6p21.3.
Adams and Barton (2007) reviewed the clinical features, pathophysiology, and management of hemochromatosis.
Genetic Heterogeneity of Hemochromatosis
At least 4 additional iron overload disorders labeled hemochromatosis have been identified on the basis of clinical, biochemical, and genetic characteristics. Juvenile hemochromatosis, or hemochromatosis type 2 (HFE2), is autosomal recessive and is divided into 2 forms: HFE2A (602390), caused by mutation in the HJV gene (608374) on chromosome 1q21, and HFE2B (613313), caused by mutation in the HAMP gene (606464) on chromosome 19q13. Hemochromatosis type 3 (HFE3; 604250), an autosomal recessive disorder, is caused by mutation in the TFR2 gene (604720) on chromosome 7q22. Hemochromatosis type 4 (HFE4; 606069), an autosomal dominant disorder, is caused by mutation in the SLC40A1 gene (604653) on chromosome 2q32. Hemochromatosis type 5 (HFE5; 615517) is caused by mutation in the FTH1 gene (134770) on chromosome 11q12.