Excessive iron stores exceed the body's capacity to chelate iron, and free iron accumulates. This unbound iron promotes free radical formation in cells, resulting in membrane lipid peroxidation and cellular injury. All of these complications, however, are much more commonly seen in persons who do not have HHC, so without a family history or iron studies, HHC will not be suspected. It should be noted that, thoughout most of human history, the average lifespan was not great enough to allow manifestation of HHC, so the appearance of persons with complications of HHC is a relatively modern phenomenon. The diagnosis of HHC depends upon documenting excessive iron storage.
Serum ferritin is also a good indicator of the amount of storage iron in the body.
The most common causes of death in individuals with HHC are hepatocellular carcinoma associated with cirrhosis, hepatic failure, and cardiac failure. There appears to be a subgroup of young patients who present with severe cardiac involvement and in whom outcome is poor as a result of congestive heart failure if they remain untreated. The gene associated with HHC is located on chromosome 6. This locus is associated with the HLA A-3 antigen. HFE gene testing for the C282Y mutation is a cost-effective method of screening relatives of patients with herediatary hemochromatosis.