Abstract

Population screening for hereditary hemochromatosis has traditionally been performed by determining the serum transferrin saturation. With the recognition that the penetrance of HFE hemochromatosis is extremely low, it has become apparent that population screening with 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. Although the factors that cause a subset of patients to develop the severe disease phenotype have not been identified, it is clear from at least three independent studies that only patients with serum ferritin concentrations of over 1000 ng/ml are at risk. We have utilized data from the Scripps-Kaiser hemochromatosis study to model results of a screening program using this ferritin cut-off value. Among 29,699 white subjects screened, only 59 had serum ferritin levels of greater than 1000 ng/ml. Twenty-four of these had homozygous mutant or compound heterozygous mutant HFE genotypes that could account for the ferritin levels. Among the remaining patients, the main causes of elevated ferritin levels were excessive alcohol intake, cancer, or liver disease. Causes for the hyperferritinemia were found in all but 8% of the 59 patients. We conclude that 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 phenotypes. Since it is clear from other longitudinal studies 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.

Author notes

Disclosure: No relevant conflicts of interest to declare.