HEREDITARY HEMOCHROMATOSIS - GENE DISCOVERY AND ITS IMPLICATIONS FOR POPULATION-BASED SCREENING

Objective.-To evaluate the role of genetic testing in screening for he reditary hemochromatosis to help guide clinicians, policymakers, and r esearchers. Participants.-An expert panel was convened on March 3, 199 7, by the Centers for Disease Control and Prevention (CDC) and the Nat ional Human Genome Research Institute (NHGRI), with expertise in epide miology, genetics, hepatology, iron overload disorders, molecular biol ogy, public health, and the ethical, legal, and social implications su rrounding the discovery and use of genetic information. Evidence.-The group reviewed evidence regarding the clinical presentation, natural h istory, and genetics of hemochromatosis, including current data on the candidate gene for hemochromatosis (HFE) and on the ethical and healt h policy implications of genetic testing for this disorder. Consensus Process.-Consensus was achieved by group discussion confirmed by a voi ce vote. A draft of the consensus statement was prepared by a writing committee and subsequently reviewed and revised by all members of the expert group over a 1-year period. Conclusions.-Genetic testing is not recommended at this time in population-based screening for hereditary hemochromatosis, due to uncertainties about prevalence and penetrance of HFE mutations and the optimal care of asymptomatic people carrying HFE mutations. In addition, use of a genetic screening test raises co ncerns regarding possible stigmatization and discrimination. Tests for HFE mutations may play a role in confirming the diagnosis of heredita ry hemochromatosis in persons with elevated serum iron measures, but e ven this use is limited by uncertainty about genotype-phenotype correl ations. To address these questions, the expert group accorded high pri ority to population-based research to define the prevalence of HFE mut ations, age and sex-related penetrance of different HFE genotypes, int eractions between HFE genotypes and environmental modifiers, and psych osocial outcomes of genetic screening for hemochromatosis.