title: The iron reabsorption index: a new phenotypic and pathophysiological descriptor in HFE hemochromatosis.
abstract: BACKGROUND
  The current phenotypic descriptors of high Fe gene hemochromatosis are hardly specific and time dependent in a context of highly variable expressivity. We hypothesized that the rate of iron removed during maintenance therapy and corresponding to the iron reabsorption index (IRI) could be patient specific and may then represent a new useful phenotypic marker.
  
  
  OBJECTIVE
  The present study aimed to describe IRI with respect to its phenotypic specificity and to its potential usefulness.
  
  
  METHODS
  We studied a cohort of 316 p.Cys282Tyr homozygous patients with stable low serum ferritin levels on maintenance therapy for at least 12 months. Characteristics at diagnosis, date and volume of phlebotomies, and parameters of iron metabolism throughout maintenance therapy were determined.
  
  
  RESULTS
  IRI ranged from 1.3 to 6.1 mg/day (median: 2.44). It was lower in women (difference: 1.26 mg/day), mainly explained by physiological blood loss, weight, and alcohol consumption. IRI was correlated to iron burden and fibrosis stage at diagnosis, was stable over time (variation: 11.5%), and depended on serum ferritin level during therapy.
  
  
  CONCLUSIONS
  Its independence from disease duration, its stability, its wide distribution, and its significant correlation with iron burden markers make IRI a valuable potential phenotypic indicator of the daily iron overabsorption in hemochromatosis. Moreover, IRI provides a conceptual frame for empiric adaptation of maintenance therapy.
authors.affiliation: aINSERM, CIC 0203, Rennes University Hospital bINSERM, U991 cPontchaillou Hospital, Department of Hepatic Diseases dPontchaillou Hospital, Department of Medical Information eHealth College, University of Rennes 1, Rennes, France.
authors.forename: Ghislain
authors.initials: G
authors.lastname: Manet
authors.forename: Edouard
authors.initials: E
authors.lastname: Bardou-Jacquet
authors.forename: Michèle
authors.initials: M
authors.lastname: Perrin
authors.forename: Jeff
authors.initials: J
authors.lastname: Morcet
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Sinteff
authors.forename: Fabrice
authors.initials: F
authors.lastname: Lainé
authors.forename: Romain
authors.initials: R
authors.lastname: Moirand
authors.forename: Yves
authors.initials: Y
authors.lastname: Deugnier
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution; D015331:Cohort Studies; D005260:Female; D005293:Ferritins / Q000097:blood; D005500:Follow-Up Studies; D006432:Hemochromatosis / Q000097:blood* / Q000235:genetics / Q000503:physiopathology / Q000628:therapy; D000071020:Hemochromatosis Protein; D006454:Hemoglobins / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D006801:Humans; D007501:Iron / Q000097:blood*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D010641:Phenotype; D018962:Phlebotomy; D055815:Young Adult
chemical_list: C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D006454:Hemoglobins; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D005293:Ferritins; D007501:Iron