Hemochromatosis: Clinical Implications

Paul C. Adams, MD, Professor of Medicine, London Health Sciences Centre, London, Ontario, Canada

In This Article


Hemochromatosis is the most common genetic disease in populations of European ancestry. Despite estimates of occurrence in different countries ranging from 1 in 100 to 1 in 300, many physicians consider hemochromatosis to be a rare disease. The diagnosis can be elusive because of the nonspecific nature of the symptoms and is rare because of the incomplete penetrance of the genotype. With the discovery of the hemochromatosis gene (HFE) in 1996 [1] have come new insights into the pathogenesis of the disease and new diagnostic strategies. Also since the discovery of the HFE gene, the question of whether hemochromatosis should be defined strictly on phenotypic criteria (such as the degree of iron overload [transferrin saturation, ferritin level, liver biopsy, hepatic iron concentration, iron removed by venesection therapy]) or as a genetic disease that is most commonly associated with the C282Y mutation and varying degrees of iron overload has come to the fore. Because the genetic test for the mutation has been widely used as a diagnostic tool, most studies now employ a combination of phenotypic and genotypic criteria for the diagnosis of hemochromatosis. It is important to realize that there are many causes of iron overload other than hemochromatosis ( Table 1 ).