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

Abstract

Early diagnosis and treatment of hemochromatosis is essential to prevent organ damage. Screening strategies to detect early hemochromatosis include testing for iron overload and/or genetic testing. Voluntary blood donors numbering 5,211 were screened with unbound iron-binding capacity (UIBC), transferrin saturation (TS), and genetic testing for the C282Y mutation of the HFE gene. The study found 16 C282Y homozygotes (1 in 327), 69 compound heterozygotes, 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 mol/L) and TS (48% ؎ 17%) in homozygotes were significantly different from compound heterozygotes, simple heterozygotes, and normals (ANOVA). Only 3 homozygotes had an elevated serum ferritin. Family studies found an additional 4 iron-loaded homozygotes. Optimal thresholds were Յ28 mol/L for UIBC and Ն46% for TS. Receiver operating characteristic (ROC) curve analysis showed an area under the curve for UIBC of 0.93 (0.85-1.0, 95% confidence interval), and for TS of 0.83 (0.7-0.95). Screening with UIBC to preselect those for genotyping is a cost-efficient strategy for population screening for hemochromatosis.

Relationship between transferrin saturation and iron stores in the African American and US Caucasian populations: analysis of data from the third National Health and Nutrition Examination Survey

“…Even among Cys282Tyr homozygotes there is considerable variability in disease expression, 22,47 and the place of testing for the Cys282Tyr mutation in screening for hemochromatosis has not been determined. Although serum ferritin concentration was once suggested as a screening marker for homozygosity for the hemochromatosis allele, 48 transferrin saturation has been regarded for some time as the best single screening test for hemochromatosis.…”

Screening for hemochromatosis

“…8 They found 16 C282Y homozygotes in their study population and claimed that UIBC performed better than transferrin saturation and was cost effective in identifying persons who should be genotyped. These findings should be considered in the context of a recent report from our center in which the cost per case detected using a similar strategy was $AUS 2,268 (approximately $US 1,500).…”

“…The investigators claim that UIBC was a considerably less expensive test than TIBC saturation and performed better than TIBC saturation in identifying C282Y homozygotes. 8 It is difficult to understand why there is such a cost advantage for UIBC over TIBC saturation when the tests differ only by the measurement of serum iron; the additional cost of measuring serum iron, when a UIBC has already been requested, is only a few cents. We also believe that it is questionable to extrapolate comparisons of test performance of UIBC and TIBC saturation in predicting homozygosity for C282Y from blood donors to the rest of the population because phlebotomy is the treatment of the disease under consideration.…”

The prevalence of primary hereditary hemochromatosis in central Anatolia

“…Screening studies for HH have been conducted on various groups such as workers (25,26), volunteer blood donors (27,28), patients followed in a hospital (29,30), and people who are living in a particular geographic region (14). In order to minimize the patient contact, outpatient population who came to the hospital for any reason were screened.…”