Haemochromatosis: understanding the mechanism of disease and implications for diagnosis and patient management following the recent cloning of novel genes involved in iron metabolism

Haemochromatosis, a common recessive genetic disorder in people of Northern European descent, is an iron storage disorder characterized by excessive hepatic iron accumulation resulting from disruption of the regulation of intestinal iron absorption. The identification of novel genes involved in the control of iron absorption from the diet has allowed improved understanding of iron metabolism in health and disease. In particular, the identification of the haemochromatosis gene (HFE) and more recently the transferrin receptor 2 gene (TfR2) together with the specific mutations in these genes which result in hepatic iron overload, has enhanced our understanding of the pathophysiology of haemochromatosis. However, because of the wide variation in phenotypic expression of the disease, there now exists a considerable challenge to diagnosis and patient management.