Genetic hemochromatosis: pathogenesis, diagnosis, and therapy

Genetic hemochromatosis is an autosomal recessive disease characterized by increased intestinal iron absorption and consequent tissue iron overload. The hemochromatosis gene has been localized on the short arm of chromosome 6, in close proximity to the HLA locus, but has yet to be identified. Neither the gene product nor the pathogenetic defect have been characterized. Clinical manifestations vary according to the degree of iron overload, ranging from the asymptomatic state to the features of cirrhosis and hepatocellular carcinoma. Early diagnosis remains essential, since the survival of patients without established cirrhosis is comparable to that of the general population. Transferrin saturation and ferritin levels are suggestive of the diagnosis, but measurement of the hepatic iron concentration still remains the gold standard, despite the utilization of computerized tomography and magnetic resonance imaging. Routine phlebotomies constitute the principal therapeutic option, despite the recent preliminary data on oral iron chelators.