The American College of Physicians (ACP) has announced, in its recommendation on screening for hereditary hemochromatosis (HH), that there is not enough evidence to recommend either for or against routine testing for this iron-overload disorder in the U.S. In its Practice Guideline of October 4, 2005, the ACP explained that the benefits of population-wide screening in the U.S. for this inherited condition have not been proven to clearly outweigh the risks and costs.

To endorse routine screening (testing of people who have no signs or symptoms of a disease) in the primary care setting, the ACP says, “one must demonstrate that the disease is common, the burden is substantial, the treatment is efficacious, the screening tests are accurate, the screening is effective, and the benefits outweigh the risks.” Hereditary hemochromatosis meets many of these criteria, but it is not clear that benefits outweigh the risks. The guidelines also discuss “case finding” (testing in persons with signs or symptoms that might be due to the disease or to some other cause) and while the evidence is also not clear, ACP supports testing in this setting. If a physician decides to do either screening or case finding, the guidelines suggest measurement of ferritin and transferrin saturation.

Hereditary hemochromatosis, also called iron overload disease, is one of the most common genetic traits among the American population, particularly among Northern European descendants. In the disease, there is progressive buildup of iron in tissues and organs. The accumulation of excess iron can lead to organ dysfunction and failure. Early treatment to remove excess iron can successfully prevent buildup of iron and avert the progression to organ failure.

Conventional blood tests - transferrin saturation and serum ferritin - are considered the primary diagnostic tests for HH. They can detect the disorder in its early stages before serious complications develop and when therapy can be successfully initiated. These tests cannot detect someone at risk. The accumulation of excess iron must be underway for these tests to detect HH.

The introduction of a genetic test for the defective gene for HH has kindled interest in screening of asymptomatic individuals to identify them before accumulation of iron actually begins. However, since not everyone with these mutations develops the disease, the implications of a positive test are not known [see Pros and Cons of Genetic Testing]. The absence of information on what to do if someone has the defective gene is one reason the medical community has not embraced population-wide screening. The guidelines suggest that physicians should discuss risks and benefits of genetic tests with those having either a family history of hemochromatosis or in persons with elevated ferritin or transferrin saturation.

Sources
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Schmitt B, Bolum RM, Green R. Screening primary care patients for hereditary hemochromatosis with transferring saturation and serum ferritin level: systematic review for the American College of Physicians. Ann Intern Med. 4 Oct 2005;143(7):146. Available on the Internet at http://www.annals.org/cgi/content/full/143/7/522. Accessed 2 Nov 2005.

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Qaseem A, Aronson M, Fitterman N, Snow V, Weiss KB, Owens DK (for the Clincial Efficacy Assessment Subcommitee of the American College of Physicians). Screening for hereditary hemochromatosis: a clinical practice guideline from the American College of Physicians. Ann Intern Med. 4 Oct 2005;143(7):517-521. Available on the Internet at http://www.annals.org/cgi/content/full/143/7/517. Accessed 26 Oct 2005.

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Tavill AS (for the American Association for the Study of Liver Diseases). Diagnosis and management of hemochromatosis. Hepatology. May 2001;33(5):1321-8. Available on the Internet at http://www.guidelines.gov/summary/summary.aspx?ss=15&doc_id=3448&nbr=002674&string=hemochromatosis. Accessed 1 Nov 2005.

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Screening for hereditary hemochromatosis: recommendations from the American College of Physicians (summaries for patients). Ann Intern Med. 4 Oct 2005;143(7):I-46. Available on the Internet at http://www.annals.org/cgi/content/full/143/7/I-46. Accessed 26 Oct 2005.

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Genetic testing. North Carolina Center for Genomics and Public Health. Available on the Internet at http://www.sph.unc.edu/nccgph/phgenetics/testing.htm. Accessed 1 Nov 2005.