Screening for hereditary hemochromatosis: a systematic review for the U.S. Preventive Services Task Force

Ann Intern Med. 2006 Aug 1;145(3):209-23. doi: 10.7326/0003-4819-145-3-200608010-00009.


Background: The U.S. Preventive Services Task Force (USPSTF) has not previously considered screening for hereditary hemochromatosis for a recommendation as a clinical preventive service for primary care clinicians.

Purpose: To conduct a focused systematic review of hereditary hemochromatosis screening relating to 2 USPSTF criteria, the burden of suffering and the potential effectiveness of a preventive intervention, to determine whether evidence is sufficient for a USPSTF recommendation.

Data sources: MEDLINE, CINAHL, and Cochrane Library databases from 1966 through February 2005. The authors supplemented literature searches with source materials from experts in the field and the bibliographies of key reviews and included studies.

Study selection: Studies were retrieved to answer 3 key questions: 1) What is the risk for developing clinical hemochromatosis among those with a homozygous C282Y genotype? 2) Does earlier therapeutic phlebotomy of individuals with primary iron overload due to hereditary hemochromatosis reduce morbidity and mortality compared with treatment after diagnosis in routine clinical care? 3) Are there groups at increased risk for developing hereditary hemochromatosis that can be readily identified before genetic screening? The authors critically appraised studies using quality criteria specific to their design.

Data extraction: The authors abstracted all studies into evidence tables using condition definitions and diagnostic criteria.

Data synthesis: Data were insufficient to define a very precise estimate of penetrance. Available data suggest that up to 38% to 50% of C282Y homozygotes may develop iron overload, with up to 10% to 33% eventually developing hemochromatosis-associated morbidity. Prevalence of C282Y homozygosity is higher in family members of probands and other high-risk patient groups defined by signs, symptoms, and phenotypic screening.

Limitations: This review considered genetic screening for HFE-related hereditary hemochromatosis in C282Y homozygotes only. Available research is limited, is based solely on observational designs, and is plagued by poor or inconsistent reporting.

Conclusions: Research addressing genetic screening for hereditary hemochromatosis remains insufficient to confidently project the impact of, or estimate the benefit from, widespread or high-risk genetic screening for hereditary hemochromatosis.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review
  • Systematic Review

MeSH terms

  • Cost of Illness
  • Evidence-Based Medicine
  • Genetic Testing* / economics
  • Genetic Testing* / ethics
  • Hemochromatosis / diagnosis*
  • Hemochromatosis / genetics
  • Hemochromatosis / therapy
  • Homozygote
  • Humans
  • Penetrance
  • Phlebotomy
  • Risk Factors