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For further information, see CMDT Part 16-13: Hemochromatosis
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Essentials of Diagnosis
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Usually suspected because of elevated iron saturation or serum ferritin or a family history
Most patients are asymptomatic
Hepatic abnormalities and cirrhosis, heart failure, hypogonadism, and arthritis
The disease is rarely recognized clinically before the fifth decade
HFE gene mutation (usually C282Y/C282Y) is found in most cases
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General Considerations
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Increased accumulation of iron as hemosiderin in the liver, pancreas, heart, adrenals, testes, pituitary, and kidneys
Autosomal recessive disease
About 85% of persons with well-established hemochromatosis are homozygous for the C282Y mutation
Population studies have shown an increased prevalence of liver disease but not of diabetes, arthritis, or heart disease in C282Y homozygotes
Hemochromatosis develops in 1–2% of C282Y/H63D compound heterozygotes
Heterozygotes do not develop cirrhosis in the absence of associated disorders such as viral hepatitis or nonalcoholic fatty liver disease
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The onset of clinical manifestations is usually after age 50—earlier in men than in women
Early symptoms are nonspecific (eg, fatigue, arthralgia)
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Later clinical manifestations
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Arthropathy (and the need for joint replacement surgery), hepatomegaly, and evidence of hepatic dysfunction
Skin pigmentation (combination of slate gray due to iron and brown due to melanin, sometimes resulting in a bronze color)
Cardiac enlargement with or without heart failure or conduction defects, diabetes mellitus with its complications, and erectile dysfunction in men
Bleeding from esophageal varices
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Differential Diagnosis
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Hepatomegaly due to other causes, eg, fatty liver
Diabetes mellitus due to other causes, eg, Cushing syndrome
Cardiac infiltrative disease due to other causes, eg, amyloidosis, sarcoidosis
Arthritis due to other causes, eg, rheumatoid arthritis, pseudogout
Hyperpigmentation due to other causes, eg, hyperbilirubinemia
Cirrhosis due to other causes
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Mildly abnormal liver chemistries (aspartate aminotransferase [AST], alkaline phosphatase)
An elevated plasma iron with > 45% transferrin saturation
An elevated serum ferritin (although a normal iron saturation or a normal ferritin does not exclude the diagnosis)
Affected men are more likely than affected women to have an elevated ferritin level
Testing for HFE mutations is indicated in any patient with evidence of iron overload
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