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OBJECTIVE:Unsaturated iron binding capacity (UIBC) has been proposed as an inexpensive alternative to transferrin saturation for detection of hereditary hemochromatosis. The aim of this study was to compare, in a hospital referral clinic, the reliability of transferrin saturation and UIBC for detection of subjects who have inherited HFE (HLA-asociated iron overload) genotypes predisposing to iron overload.METHODS:Serum transferrin saturation, UIBC, and ferritin were tested in 110 consecutive subjects. Optimum thresholds were determined from receiver operating characteristic curves.RESULTS:Of 110 subjects, 44 carried significant HFE mutations (C282Y/C282Y or C282Y/H63D). In genetically predisposed subjects with biochemical expression, the optimum threshold for transferrin saturation was 43%, giving a sensitivity of 0.88 and specificity 0.95. For UIBC, the optimum threshold was 143 μg/dL (25.6 μmol/L), giving a sensitivity of 0.91 and specificity of 0.95. In patients referred with a family history or clinical suspicion of hemochromatosis, transferrin saturation and UIBC were highly reliable predictors of genotype. In patients referred for investigation of abnormal liver enzymes without a known family history of hemochromatosis, a normal transferrin saturation or normal UIBC was highly reliable in excluding hemochromatosis.CONCLUSIONS:Transferrin saturation and UIBC have equal reliability in ability to predict hemochromatosis. UIBC should be considered as an alternative to transferrin saturation in detection of hemochromatosis. [Copyright &y& Elsevier]