Iron overload, public health, and genetics: Evaluating the evidence for hemochromatosis screening

Population screening for hemochromatosis done by using the transferrin satu ration test has been advocated by experts to permit the initiation of thera peutic phlebotomy before the onset of clinical disease. The discovery of a gene associated with hemochromatosis has made DNA testing another option fo r screening and diagnosis. In this paper, U.S. Preventive Services Task For ce criteria are used to evaluate the evidence for the usefulness of populat ion screening done by using iron measures or genetic testing. Published clinical research offers little evidence to suggest that populati on screening for hemochromatosis done by using genetic testing improves cli nical outcomes. Although one recently discovered mutation, C282Y, accounts for 60% to 92% of cases of the disease in series of patients with hemochrom atosis, uncertainties remain about the clinical penetrance of various genot ypes; the accuracy of genetic testing; and the ethical, legal, and social e ffects of genetic testing. Before population screening for hemochromatosis done by using transferrin saturation testing can be recommended, laboratory standardization needs to be addressed and questions about risk for clinica l disease in asymptomatic persons with mutations or early biochemical expre ssion of disease require resolution. Evidence from case series suggests tha t hemochromatosis may be associated with liver cancer, other liver disease, diabetes, bradyarrhythmias, and arthritis. In ail studies but one, however , estimation of the magnitude and significance of this risk is limited by l ack of adequate comparison groups. The need for population data to answer q uestions about penetrance among asymptomatic persons should not impede effo rts to increase the detection and treatment of hemochromatosis in persons f ound to have elevated iron measures, a family history of hemochromatosis, o r consistent early signs and symptoms of the disease.