Features of hereditary hemochromatosis include cirrhosis of the liver, diabetes, hyperpigmentation of the skin, heart failure and hepatocellular carcinoma. Traditionally, serum ferritin, transferrin saturation and hepatic iron have been used to diagnosis this condition clinically. Preclinical disease is more difficult to detect by these methods, with results being dependent on age, gender and diet. Molecular analysis detects individuals at risk for developing hemochromatosis independent of these factors. Mutation detection, however, does not predict severity of disease or age of onset.
Presymptomatic detection is important since treatment can prevent organ damage.
Treatment for both symptomatic and presymptomatic patients consists of therapeutic phlebotomy. The clinical significance of the second mutation, H63D, is unknown, but is thought to contribute to a mild form of the disease. Compound heterozygotes for C282Y and H63D and homozygotes for the H63D have been described with some individuals showing mild symptoms, although most have no detectable symptoms of hemochromatosis. Hemochromatosis mutation detection is indicated for patients with increased serum ferritin levels, transferrin saturation, or cirrhosis of the liver. Family members of individuals diagnosed with hemochromatosis should also be tested to detect subclinical cases.