Population screening for hemochromatosis: A comparison of unbound iron-binding capacity, transferrin saturation, and C282Y genotyping in 5,211 voluntary blood donors

Early diagnosis and treatment of hemochromatosis is essential to prevent or gan damage. Screening strategies to detect early hemochromatosis include te sting for iron overload and/or genetic testing. Voluntary blood donors numb ering 5,211 were screened with unbound iron-binding capacity (UIBC), transf errin saturation (TS), and genetic testing for the C282Y mutation of the HF E gene. The study found 16 C282Y homozygotes (1 in 327), 69 compound hetero zygotes, 371 simple heterozygotes, and 4,755 normals. There were 5 men and 11 women homozygotes with a mean age of 42, range 28 to 57. Mean UIBC (24 /- 7 mu mol/L) and TS (48% +/- 17%) in homozygotes were significantly diffe rent from compound heterozygotes, simple heterozygotes, and normals (ANOVA) . Only 3 homozygotes had an elevated serum ferritin. Family studies found a n additional 4 iron-loaded homozygotes. Optimal thresholds were less than o r equal to 28 mu mol/L for UIBC and greater than or equal to 46% for TS. Re ceiver operating characteristic (ROC) curve analysis showed an area under t he curve for UIBC of 0.93 (0.85-1.0, 95% confidence interval), and for TS o f 0.83 (0.7-0.95). Screening with UIBC to preselect those for genotyping is a cost-efficient strategy for population screening for hemochromatosis.