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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 282nd
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.
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