Hereditary hemochromatosis: gene discovery and its implications for population-based screening

JAMA. 1998 Jul 8;280(2):172-8. doi: 10.1001/jama.280.2.172.


Objective: To evaluate the role of genetic testing in screening for hereditary hemochromatosis to help guide clinicians, policymakers, and researchers.

Participants: An expert panel was convened on March 3, 1997, by the Centers for Disease Control and Prevention (CDC) and the National Human Genome Research Institute (NHGRI), with expertise in epidemiology, genetics, hepatology, iron overload disorders, molecular biology, public health, and the ethical, legal, and social implications surrounding the discovery and use of genetic information.

Evidence: The group reviewed evidence regarding the clinical presentation, natural history, and genetics of hemochromatosis, including current data on the candidate gene for hemochromatosis (HFE) and on the ethical and health policy implications of genetic testing for this disorder.

Consensus process: Consensus was achieved by group discussion confirmed by a voice 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 concerns regarding possible stigmatization and discrimination. Tests for HFE mutations may play a role in confirming the diagnosis of hereditary hemochromatosis in persons with elevated serum iron measures, but even this use is limited by uncertainty about genotype-phenotype correlations. To address these questions, the expert group accorded high priority to population-based research to define the prevalence of HFE mutations, age and sex-related penetrance of different HFE genotypes, interactions between HFE genotypes and environmental modifiers, and psychosocial outcomes of genetic screening for hemochromatosis.

Publication types

  • Consensus Development Conference
  • Review

MeSH terms

  • Female
  • Genetic Testing
  • Genotype
  • HLA Antigens / genetics*
  • Hemochromatosis / diagnosis*
  • Hemochromatosis / epidemiology
  • Hemochromatosis / genetics*
  • Hemochromatosis / physiopathology
  • Hemochromatosis Protein
  • Histocompatibility Antigens Class I / genetics*
  • Humans
  • Male
  • Membrane Proteins*
  • Mutation
  • Practice Guidelines as Topic


  • HFE protein, human
  • HLA Antigens
  • Hemochromatosis Protein
  • Histocompatibility Antigens Class I
  • Membrane Proteins