Hereditary hemochromatosis is a disorder that causes the body to absorb too much iron from the diet. The excess iron is stored in the body’s tissues and organs, particularly the skin, heart, liver, pancreas, and joints. Because humans cannot increase the excretion of iron, excess iron can overload and eventually damage tissues and organs. For this reason, hereditary hemochromatosis is also called an iron overload disorder.


Early symptoms of hereditary hemochromatosis may include extreme tiredness (fatigue), joint pain, abdominal pain, weight loss, and loss of sex drive. As the condition worsens, affected individuals may develop arthritis, liver disease (cirrhosis) or liver cancer, diabetes, heart abnormalities, or skin discoloration. The clinical manifestations of iron overload typically develop in the 40s or 50s. The appearance and severity of symptoms can be affected by environmental and lifestyle factors such as the amount of iron in the diet, alcohol use, and infections.


Hereditary hemochromatosis is most commonly caused by certain variants in the HFE gene.

There are four types of hereditary hemochromatosis, which are categorized by the specific gene mutation involved (Table 1).

Homozygous C282Y and heterozygous C282Y/H63D mutations of the HFE gene (iron regulatory protein) on chromosome 6 are responsible for up to 95% of hereditary hemochromatosis cases (type 1).

Hereditary hemochromatosis types 2 to 4 comprise the small percentage of remaining cases and are caused by non- HFE mutations.

Despite the high prevalence of the gene mutation, there is a low and variable clinical penetrance, with up to 25% of people with C282Y homozygosity being clinically asymptomatic.