Evelyn P. Whitlock, MD, MPH; Betsy A. Garlitz, MD; Emily L. Harris, PhD, MPH; Tracy L. Beil, MS; Paula R. Smith, RN, BSN
Disclaimer: The authors of this article are responsible for its contents, including any clinical or treatment recommendations. No statement in this article should be construed as an official position of the U.S. Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services.
Acknowledgments: The authors thank Kevin Lutz, MFA, and Taryn Cardenas for their help in preparing this manuscript, and Daphne Plaut, MLS, for conducting the literature searches. They also thank the USPSTF, AHRQ staff, and expert reviewers for their contribution to this project.
Grant Support: This study was conducted by the Oregon Evidence-based Practice Center under contract to the Agency for Healthcare Research and Quality, Rockville, Maryland (contract 290-02-0024, task order no. 2).
Potential Financial Conflicts of Interest: None disclosed.
Requests for Single Reprints: Reprints are available from the Agency for Healthcare Research and Quality Web site (www.preventiveservices.ahrq.gov) and through the Agency for Healthcare Research and Quality Publications Clearinghouse (telephone, 800-358-9295).
Current Author Addresses: Drs. Whitlock and Harris, Ms. Beil, and Ms. Smith: Center for Health Research, Kaiser Permanente, 3800 North Interstate Avenue, Portland, OR 97227-1110.
Dr. Garlitz: Oregon Health Sciences University, 3181 SW Sam Jackson Park Road, Portland, OR 97239-3098.
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.
To conduct a focused systematic review of heredita-ry hemochromatosis screening relating to 2 USPSTF criteria, the burden of suffering and the potential effectiveness of a preven-tive intervention, to determine whether evidence is sufficient for a USPSTF recommendation.
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.
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.
The authors abstracted all studies into evidence tables using condition definitions and diagnostic criteria.
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.
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.
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.
Search results and article flow by key question.
Table 1. Screening and Diagnostic Criteria for Iron Overload
Table 2. Genotypic Screening Yields*
Table 3. Summary of Treatment Trials: Key Question 2*
Table 4. Prevalence of C282Y Homozygosity in High-Risk Groups*
Table 5. Summary of Overall Evidence
Whitlock EP, Garlitz BA, Harris EL, et al. Screening for Hereditary Hemochromatosis: A Systematic Review for the U.S. Preventive Services Task Force. Ann Intern Med. 2006;145:209–223. doi: https://doi.org/10.7326/0003-4819-145-3-200608010-00009
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Published: Ann Intern Med. 2006;145(3):209-223.
Gastroenterology/Hepatology, Guidelines, Liver Disease, Prevention/Screening.
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