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 Blood, 1 April 2008, Vol. 111, No. 7, pp. 3373-3376.
Prepublished online as a Blood First Edition Paper on November 19, 2007; DOI 10.1182/blood-2007-07-102673.

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CLINICAL TRIALS AND OBSERVATIONS

Screening for hemochromatosis by measuring ferritin levels: a more effective approach

Jill Waalen1, Vincent J. Felitti2, Terri Gelbart1, and Ernest Beutler1

1 Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA; and 2 Kaiser Permanente Medical Care Program, San Diego, CA

Because the penetrance of HFE hemochromatosis is low, traditional population screening measuring the transferrin saturation is unlikely to be cost-effective because the majority of subjects detected neither have clinical disease nor are likely to develop it. Three independent studies show that only patients with serum ferritin concentrations more than 1000 µg/L are at risk for cirrhosis, one of the main morbidities of hemochromatosis. Among 29 699 white subjects participating in the Scripps/Kaiser hemochromatosis study, only 59 had serum ferritin levels more than 1000 µg/L; 24 had homozygous mutant or compound heterozygous mutant HFE genotypes. In all but 5 of the other subjects, the causes of elevated ferritin were excessive alcohol intake, cancer, or liver disease. Screening for hemochromatosis with serum ferritin levels will detect the majority of patients who will be clinically affected and may detect other clinically significant disease in patients who do not have hemochromatosis genotypes. Because the ferritin level of the majority of adult homozygotes for HFE mutations does not rise over long periods of time, excluding subjects with serum ferritin levels less than or equal to 1000 µg/L should not result in missed opportunities for early treatment of patients who could benefit.


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