Hemochromatosis and cancer
Hemochromatosis is a metabolic disorder characterized by excess iron accumulation in various organs, including the liver, heart, and pancreas. This condition can be genetic, often arising from mutations in the HFE gene, leading to an increased absorption of dietary iron. Notably, hereditary hemochromatosis is more prevalent among individuals of European descent. Symptoms may include fatigue, joint pain, and decreased libido, typically emerging after age forty in men and age fifty in women; however, some individuals remain asymptomatic.
The excess iron can cause serious complications, including liver damage, diabetes, and increased risk of liver cancer. Diagnosis involves blood tests to measure iron levels and genetic testing for HFE mutations, while imaging studies may assess liver iron content. Treatment focuses on therapeutic phlebotomy to reduce iron levels and may involve lifestyle changes to avoid iron-rich foods and supplements. Early detection and management are crucial to prevent organ damage and related complications, highlighting the importance of understanding hemochromatosis for those at risk.
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Subject Terms
Hemochromatosis and cancer
ALSO KNOWN AS: Bronze diabetes; hereditary, familial, genetic, primary, or type 1, 2, 3, or 4 hemochromatosis; iron overload; Troisier-Hanot-Chauffard syndrome
RELATED CONDITIONS: Liver cancer, heart disease, impotence, infertility, premature menopause, diabetes, arthritis, cirrhosis, bronze skin
DEFINITION: Hemochromatosis is a metabolic disorder in which iron accumulates in the liver, heart, skin, pancreas, and other organs. Once iron is absorbed, the only way the body can excrete the excess iron is through bleeding.
Hemochromatosis may be genetic or nongenetic. Nongenetic sources include excess deposition of iron in the tissues due to multiple transfusions, chronic liver disease, excessive iron intake, or megadoses of vitamin C, which promotes iron absorption. Types 1, 2, and 3 can be inherited in an autosomal recessive pattern, as with homozygous mutations in the HFE gene. The most common HFE gene mutation is C282Y, followed by H63D. Type 2 results from mutations in HJV or HAMP genes, type 3 results from TFR2 gene mutations, and type 4 results from mutations in the SLC40A1 gene.
Risk factors: Hereditary hemochromatosis is most prevalent among persons of European descent. Not everyone who demonstrates the HFE mutation will develop hemochromatosis.
Etiology and the disease process: The HFE gene normally codes for the intestinal transmembrane glycoprotein that regulates dietary iron absorption. A mutation causes the system to deposit more iron in the organs than needed, leading to increased absorption and an overload of unbound iron molecules circulating within the system. Once the body exceeds its natural limit of iron storage of ferritin molecules, the excess unbound iron molecules result in peroxidation of the lipid membrane and cellular injury.
Incidence: Type 1 hemochromatosis is one of the most common genetic disorders in the United States, impacting approximately one million adults. Types 2, 3, and 4 are rare.
Symptoms: Early symptoms of hemochromatosis include fatigue, weakness, joint pain, or decreased libido. These symptoms typically appear after age forty in men and after fifty in women, but hemochromatosis may be asymptomatic.
Screening and diagnosis: A series of fasting serum blood tests on ferritin, iron, total iron binding capacity (TIBC), unsaturated iron binding capacity (UIBC), or transferring saturation (TS) assist in the diagnosis of hemochromatosis. The TS may be calculated or measured directly by immunoassay. Genotyping may confirm if the HFE mutation is present. A liver biopsy may establish a prognosis of risk of advancing fibrosis. Magnetic resonance imaging can assess liver iron content.
Treatment and therapy: Therapeutic phlebotomy to decrease the excess iron stores is especially effective before symptoms of complications appear. Persons with hemochromatosis are also advised to avoid iron and vitamin C supplements. Liver transplant may be indicated for persons with decompensated cirrhosis due to hemochromatosis.
Prognosis, prevention, and outcomes: Early detection and therapeutic phlebotomy to maintain iron levels within established limits prevent tissue and organ complications associated with hemochromatosis. For individuals who have already experienced organ compromise, while damage is not reversible, further damage can be slowed with therapeutic phlebotomy.
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