Hereditary hemochromatosis is an inherited condition. It occurs when a person inherits two copies of a mutation in the HFE gene, one from each parent. People with one copy of an HFE mutation are carriers for the condition and usually have little or no excess accumulation of iron. However, not all people with two genetic mutations develop signs and symptoms of the disorder. It is possible that some patients become iron-overloaded after years of excess iron ingestion, but most cases are genetic.
Iron overload can also occur with repeated blood transfusions.
Although hemochromatosis was first described in the medical literature over 100 years ago, the cause of the disease iron accumulation, leading to damage of healthy tissues, was not initially known, and the disease was recognized only in its late stages. More recently, the gene associated with hereditary hemochromatosis, HFE, was identified in 1996. Several HFE mutations have been described. One of these mutations, C282Y, accounts for the majority of cases of hereditary hemochromatosis. Both serum iron measures and genetic testing are imperfect screening tools.