GENETIC HEMOCHROMATOSIS - PATHOGENESIS, DIAGNOSIS, AND THERAPY

Genetic hemochromatosis is an autosomal recessive disease characterize d by increased intestinal iron absorption and consequent tissue iron o verload. The hemochromatosis gene has been localized on the short arm of chromosome 6, in close proximity to the HLA locus, but has yet to b e identified. Neither the gene product nor the pathogenetic defect hav e been characterized. Clinical manifestations vary according to the de gree of iron overload, ranging from the asymptomatic state to the feat ures of cirrhosis and hepatocellular carcinoma. Early diagnosis remain s essential, since the survival of patients without established cirrho sis is comparable to that of the general population. Transferrin satur ation and ferritin levels are suggestive of the diagnosis, but measure ment of the hepatic iron concentration still remains the gold standard , despite the utilization of computerized tomography and magnetic reso nance imaging. Routine phlebotomies constitute the principal therapeut ic option, despite the recent preliminary data on oral iron chelators.