Before the 1980s, hemochromatosis was thought to be an uncommon disorder, but severe iron overload was common in case series of white patients diagnosed to have “classical” hemochromatosis in medical care. A high proportion of 2851 hemochromatosis patients located using patient advocacy groups, physicians, blood centers, newsletters, and the internet reported on a questionnaire that they had symptoms or other problems that were interpreted as complications of iron overload. Thus, it was generally presumed for many years that most whites with hemochromatosis would eventually develop injurious iron overload. Accordingly, large-scale population screening using iron phenotyping of white populations was promoted to achieve early diagnosis and permit timely treatment to alleviate iron overload.

A pioneering screening study of 11,065 presumably healthy Utah blood donors revealed a high prevalence of hemochromatosis homozygotes defined by a persistently high serum transferrin saturation level and post-initial screening evaluations of iron stores. Since the description of the HFE gene in 1996, it has been possible to screen for the genotype HFE C282Y homozygosity (and serum iron measures) associated with “classical” hemochromatosis. Additional large-scale genetic screening studies have been performed in southern California, Norway, North America, and Australia. Outcomes of large-scale screening programs to detect HFE hemochromatosis and iron overload are summarized herein (Table 37.1). The potential value of targeted screening is also described.

Large-scale screening programs

Utah blood donors

In a landmark study of the 1980s, 11,065 presumably healthy volunteer blood donors in Utah were screened using an elevated transferrin saturation criterion.