Biological Variability of Transferrin Saturation and Unsaturated Iron-Binding Capacity

Paul C. Adams, David M. Reboussin, Richard D. Press, James C. Barton, Ronald T. Acton, Godfrey C. Moses, Catherine Leiendecker-Foster, Gordon D. McLaren, Fitzroy W. Dawkins, Victor R. Gordeuk, Laura Lovato, John H Eckfeldt

Research output: Contribution to journalArticlepeer-review

58 Scopus citations

Abstract

Background: Transferrin saturation is widely considered the preferred screening test for hemochromatosis. Unsaturated iron-binding capacity has similar performance at lower cost. However, the within-person biological variability of both these tests may limit their ability at commonly used cut points to detect HFE C282Y homozygous patients. Methods: The Hemochromatosis and Iron Overload Screening Study screened 101,168 primary care participants for iron overload using transferrin saturation, unsaturated iron-binding capacity, ferritin, and HFE C282Y and H63D genotyping. Transferrin saturation and unsaturated iron-binding capacity were performed at initial screening and again when selected participants and controls returned for a clinical examination several months later. A missed case was defined as a C282Y homozygote who had transferrin saturation below the cut point (45% for women, 50% for men) or unsaturated iron-binding capacity above the cut point (150 μmol/L for women, 125 μmol/L for men) at the initial screening or the clinical examination, or both, regardless of serum ferritin. Results: There were 209 C282Y previously undiagnosed homozygotes with transferrin saturation and unsaturated iron-binding capacity testing performed at the initial screening and clinical examination. Sixty-eight C282Y homozygotes (33%) would have been missed at these transferrin saturation cut points (19 men, 49 women; median serum ferritin level of 170 μg/L; first and third quartiles, 50 and 474 μg/L), and 58 homozygotes (28%) would have been missed at the unsaturated iron-binding capacity cut points (20 men, 38 women; median serum ferritin level of 168 μg/L; first and third quartiles, 38 and 454 μg/L). There was no advantage to using fasting samples. Conclusions: The within-person biological variability of transferrin saturation and unsaturated iron-binding capacity limits their usefulness as an initial screening test for expressing C282Y homozygotes.

Original languageEnglish (US)
Pages (from-to)999.e1-999.e7
JournalAmerican Journal of Medicine
Volume120
Issue number11
DOIs
StatePublished - Nov 2007

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