Hemochromatosis: advances in molecular genetics and clinical diagnosis.

Hereditary hemochromatosis (HH) is a human leukocyte antigen-linked inherited disease that is characterized by inappropriately high absorption of iron by the gastrointestinal mucosa. The spectrum of disease presentation is changing with more and more patients now being identified before they are symptomatic with complications of iron overload. A candidate gene for HH, called HFE, was identified in 1996, and a test for the gene is commercially available. A review of the recent identification of the gene and its implications for clinical diagnosis and therapy is presented. We also propose an algorithm for evaluation of patients for HH. Early diagnosis and appropriate therapy can prevent significant morbidity and mortality associated with the development of end-organ complications of HH. The understanding of the C282Y and H63D mutations is still evolving, and the algorithm and the contribution of various heterozygous mutations to the diagnosis and management of iron overload need to be confirmed by further clinical and genetic studies.