Because the penetrance of HFE hemochromatosis is low, traditional population screening measuring the transferrin saturation is unlikely to be cost-effective, as the vast majority of individuals detected neither have clinical disease nor are likely to develop it.
Three independent studies show that only patients with serum ferritin concentrations over 1000 ng/ml 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 of greater than 1000 ng/ml. Twenty-four had homozygous mutant or compound heterozygous mutant HFE genotypes .
In all but 5 of the other subjects the causes of elevated ferritin was excessive alcohol intake, cancer, or liver disease. Screening for hemochromatosis with serum ferritin levels will detect the vast majority of patients who will be clinically affected, and may detect other clinically significant disease in patients who do not have hemochromatosis genotypes .
Since it is clear that the ferritin level of the vast majority of adult homozygotes for HFE mutations does not rise over long periods of time, excluding subjects with serum ferritin levels /=1000 ng/ml should not result in missed opportunities for early treatment of patients who could benefit.
Waalen J , Felitti VJ , Gelbart T , Beutler E .
Department of Molecular and Experimental Medicine , The Scripps Research Institute, La Jolla, CA, United States.