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Hereditary hemochromatosis is an autosomal recessive disorder characterized by iron overload in the liver, heart, pancreas, pituitary gland, and joints. Although the specific inherited defect remains uncertain, the gene responsible for hemochromatosis has been mapped to chromosome 6 near the human leukocyte antigen-A (HLA-A) allele hemochromatosis, hemocromatosis, hemachromatosis, hemacromatosis. The homozygote frequency is estimated from 1:400 to as high as 1:100. Patients with the disease absorb excessive amounts of iron from the gut and deposit the metal in many organs, where it injures cells. Only homozygotes develop clinically significant hepatic iron overload and
Iron accumulation is progressive from birth but rarely leads to symptoms before age 40. The onset of disease is delayed even further in females, because of loss of iron in menstrual blood and a lower intake of dietary iron. Presenting symptoms are often vague, with abdominal pain reported in as few as 16% or
Biochemical abnormalities that suggest hereditary hemochromatosis in symptomatic individuals include elevations in transferrin saturation (> 62% in males; > 50% in females) and ferritin (more than twice normal). It must be noted, however, that both of these parameters are prone to false-positive elevations and must be interpreted with caution. Transferrin saturation can be falsely elevated in nonfasting patients, in those with active liver necrosis, and even in
Ferritin also increases nonspecifically with hepatocellular necrosis and may cause particular confusion in patients with alcoholic liver disease. To diagnose hereditary hemochromatosis with certainty, a liver biopsy must be obtained to quantify total hepatic iron. Patients with hereditary hemochromatosis who have clinical evidence of liver disease will have > 10,000 µg iron per gram of dry liver tissue. Younger patients who have less pronounced increases in total hepatic iron can be distinguished from heterozygotes and from
Phlebotomy is the mainstay of therapy and can prevent or even reverse hepatic fibrosis. Fully developed cirrhosis is not usually reversible, although phlebotomy can enhance the survival of patients with cirrhosis. Unfortunately, patients with cirrhosis are at high risk of developing hepatocellular carcinoma, whether or not they undergo iron depletion. Hepatocellular carcinoma is currently the leading cause of death among patients with hereditary hemochromatosis.
Family members of probands are screened by HLA typing and by serial measurements of transferrin saturation and ferritin. Because of the high frequency of the genetic defect, screening the general population with iron studies is under review but has not been advocated to date. HLA typing has