While the association of C282Y with hereditary hemochromatosis is clear, the significance of the H63D mutation is less clear. Patients homozygous for this mutation may have increased iron stores but confounding factors are present and they do not appear at increased risk for hereditary hemochromatosis. In combination with a heterozygous C282Y, it has been shown that individuals with H63D have an increased risk of developing iron overload. In the past, a combination of blood iron measurements and liver biopsy have been used in suspected patients to establish a diagnosis of hereditary hemochromatosis. The identification of the mutations of HFE and in particular the high degree of association of C282Y with hereditary hemochromatosis provides a new, highly specific, method of evaluating individuals in which this disorder is suspected.
Routine phlebotomy prevents the accumulation of excess iron and manifestations of the disorder.
The management of heart, liver, and pancreatic failure, once established, differs little from the conventional management of these conditions. The chief causes of death in untreated patients are due to heart failure, liver cirrhosis, and hepatocellular carcinoma. Removal of excess iron via phlebotomy, and maintenance of iron stores at near-normal levels can prolong life expectancy. Many of the symptoms may improve with removal of iron, although cirrhosis, once present, is generally irreversible. Early therapy in asymptomatic patients is extremely important, and will prevent most of the manifestations of this disease.