title: Biological variability of transferrin saturation and unsaturated iron-binding capacity.
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 micromol/L for women, 125 micromol/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 microg/L; first and third quartiles, 50 and 474 microg/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 microg/L; first and third quartiles, 38 and 454 microg/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.
authors.affiliation: Department of Medicine, University Hospital, London, Ontario, Canada. padams@uwo.ca
authors.forename: Paul C
authors.initials: PC
authors.lastname: Adams
authors.forename: David M
authors.initials: DM
authors.lastname: Reboussin
authors.forename: Richard D
authors.initials: RD
authors.lastname: Press
authors.forename: James C
authors.initials: JC
authors.lastname: Barton
authors.forename: Ronald T
authors.initials: RT
authors.lastname: Acton
authors.forename: Godfrey C
authors.initials: GC
authors.lastname: Moses
authors.forename: Catherine
authors.initials: C
authors.lastname: Leiendecker-Foster
authors.forename: Gordon D
authors.initials: GD
authors.lastname: McLaren
authors.forename: Fitzroy W
authors.initials: FW
authors.lastname: Dawkins
authors.forename: Victor R
authors.initials: VR
authors.lastname: Gordeuk
authors.forename: Laura
authors.initials: L
authors.lastname: Lovato
authors.forename: John H
authors.initials: JH
authors.lastname: Eckfeldt
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005819:Genetic Markers; D006432:Hemochromatosis / Q000175:diagnosis* / Q000235:genetics; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D006720:Homozygote; D006801:Humans; D033862:Iron-Binding Proteins / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D014168:Transferrin / Q000378:metabolism*
chemical_list: D005819:Genetic Markers; C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D033862:Iron-Binding Proteins; D008565:Membrane Proteins; D014168:Transferrin