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<p><strong>You Are Here:</strong> <span class="crumb_link"><a href="/" class="crumb_link">AHRQ Archive Home</a> > <a href="/research/resarch.htm" class="crumb_link"><em>Research Activities</em> Archive</a> > <a href="." class="crumb_link">February 2001</a> </span></p>
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<td><h1><a name="h1" id="h1"></a>Clinical Decisionmaking </h1>
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<p>This information is for reference purposes only. It was current when produced and may now be outdated. Archive material is no longer maintained, and some links may not work. Persons with disabilities having difficulty accessing this information should contact us at: <a href="https://info.ahrq.gov/">https://info.ahrq.gov</a>. Let us know the nature of the problem, the Web address of what you want, and your contact information. </p>
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<h2><a name="head3">Many questions remain regarding the optimal screening strategy for hereditary hemochromatosis</a></h2>
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<p>Hereditary hemochromatosis (HHC) is a common disorder that affects from 3 to 8 of every 1,000 people. HHC patients have enhanced gastrointestinal absorption of iron and may accumulate excessive iron stores, which causes organ dysfunction. Two mutations in the HFE gene—C282Y and H63D—have been described in HHC patients. However, a new study shows that asymptomatic patients with moderate iron overload have a different genotypic profile than that seen in patients with advanced iron overload. In the study, fewer asymptomatic patients had homozygous C282Y than clinically affected (symptomatic) patients. The study was supported in part by the Agency for Healthcare Research and Quality (HS07616).</p>
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<p>Screening for HHC by means of transferrin saturation (TS) levels has been advocated and will identify many patients who are asymptomatic. However, the significance of identifying patients with modest degrees of iron loading who may not be homozygous for C282Y must be addressed if routine TS screening is to be implemented, according to the researchers.</p>
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<p>Ronald L. Sham, M.D., of Rochester General Hospital, and his colleagues determined HFE genotypes among 123 asymptomatic HHC patients referred to their clinic. They correlated the patients' genotypic profiles with the degree of iron overload and evaluated the relationship between mobilized iron (mob Fe), age, serum ferritin (SF), and quantitative hepatic iron (QHI) in this population. They also used quantitative phlebotomy to determine mob Fe and genotyping for C282Y and H63D mutations.</p>
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<p>Of the entire group, 60 percent were homozygous for C282Y, and 13 percent were compound heterozygotes (C282Y/H63D). Asymptomatic patients who had a lower iron burden frequently had genotypes other than homozygous C282Y, a different genotypic profile than those with advanced iron overload. As routine screening for HHC using TS testing becomes more commonplace, clinicians will need a comprehensive understanding of the laboratory phenotypes and genotypes that can be seen in identified patients, conclude the authors.</p>
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<p>More details are in "Asymptomatic hemochromatosis subjects: Genotypic and phenotypic profiles," by Dr. Sham, Richard F. Raubertas, Ph.D., Caroline Braggins, M.B.A., and others, in the December 1, 2000 <em>Blood</em> 96(12), pp. 3707-3711.</p>
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