HEMOCHROMATOSIS - ADVANCES IN MOLECULAR-GENETICS AND CLINICAL-DIAGNOSIS

Hereditary hemochromatosis (HH) is a human leukocyte antigen-linked in herited disease that is characterized by inappropriately high absorpti on of iron by the gastrointestinal mucosa. The spectrum of disease pre sentation is changing with more and more patients now being identified before they are symptomatic with complications of iron overload. A ca ndidate gene for HH, called HFE, was identified in 1996, and a test fo r the gene is commercially available. A review of the recent identific ation of the gene and its implications for clinical diagnosis and ther apy is presented. We also propose an algorithm for evaluation of patie nts for HH. Early diagnosis and appropriate therapy can prevent signif icant morbidity and mortality associated with the development of end-o rgan complications of HH. The understanding of the C282Y and H63D muta tions is still evolving, and the algorithm and the contribution of var ious heterozygous mutations to the diagnosis and management of iron ov erload need to be confirmed by further clinical and genetic studies.