inborn metabolic defect (metabolic disease) characterized by an increased absorption of iron, which accumulates in body tissues. The clinical manifestations include skin pigmentation, diabetes mellitus, enlargement of the spleen and liver, cirrhosis, heart failure, arthritis, and general weakness and lassitude.

There are four types of hemochromatosis. Type 1 is characterized by the appearance of symptoms in men between the ages of 40 and 60 and in women after menopause (when iron is no longer lost through menstruation and pregnancy). Type 2, also called juvenile hemochromatosis, is divided into types 2A and 2B based on different genetic mutations (mutation) and is characterized by the onset of symptoms in childhood that often lead to delayed puberty or sex hormone deficiencies. Type 3 is characterized by the onset of symptoms in adults between the ages of 20 and 30, and type 4, sometimes called ferroportin disease, is characterized by the onset of symptoms in adults around the age of 40. Types 1, 2, and 3 are autosomal recessive diseases, meaning that two copies of the mutated gene, one inherited from each parent, are required to cause disease. In contrast, type 4 is autosomal dominant, meaning that only one copy of the mutated gene is required to cause disease. Type 1 is the most common form, and nearly all individuals with type 1 hemochromatosis are of northern European descent. In fact, an estimated 1 in 8 to 1 in 12 people of this descent carry genetic mutations associated with type 1 hemochromatosis. Because of the high incidence of this defect, genetic testing is often performed in affected families to determine whether an individual is a carrier.

Mutations that cause hemochromatosis can occur in several different genes. Type 1 is caused by mutation in a gene designated HFE (hemochromatosis), which codes for hemochromatosis protein. This protein is involved in regulating the absorption of iron in the body. The interaction of hemochromatosis protein with other iron-regulating substances appears to moderate the levels of a protein called ferritin, which stores iron and is found in cells of the liver, spleen, and intestinal mucosa. Mutation in HFE leads to excess absorption of iron and to excess levels of ferritin. As a result, iron slowly accumulates in the tissues of the body.

Diagnosis of hemochromatosis is based on genetic testing, blood and serum testing, and liver biopsy. Treatment consists of phlebotomy (the removal of blood) at regular intervals to decrease the concentration of ferritin in the body. Phlebotomy may be performed once or twice a week in the initial stages of treatment; however, when ferritin levels return to normal, most patients require maintenance phlebotomy only once every one to four months.