Hereditary hemochromatosis

Hereditary hemochromatosis is an inherited disorder that increases the amount of iron that the body absorbs from the gut. Symptoms are caused by this excess iron being deposited in multiple organs of the body. Most commonly, excess iron in the liver causes cirrhosis, which may develop into liver cancer. Iron deposits in the pancreas can result in diabetes. Similarly, excess iron stores can cause cardiomyopathy, pigmentation of the skin, and arthritis.

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Many mutations in the body's iron transport system can cause hemochromatosis; however, most cases are caused by mutations in the HFE gene. This is located on chromosome 6, and one mutation leads to the substitution of the 282^nd amino acid. Cysteine becomes tyrosine, therefore the mutation is called C282Y. The switch of amino acids is thought to affect how the HFE protein interacts with the transferrin receptor (TFR1), which plays an important role in iron homeostasis. A less common mutation, H63D, has also been identified in the HFE gene.

Hemochromatosis is one of the most common autosomal recessive disorders among Caucasians in the United States; however, only a small proportion of these people suffer any symptoms. This may be attributable to both environmental (diet and blood loss) and genetic factors. Recent advances in the development of animal models that show the complications of hemochromatosis may soon provide useful tools in deciphering how other genes play a part in iron regulation.