title: Impact of HFE genetic testing on clinical presentation of hereditary hemochromatosis: new epidemiological data.
abstract: BACKGROUND
  Hereditary hemochromatosis (HH) is a common inherited disorder of iron metabolism in Northern European populations. The discovery of a candidate gene in 1996 (HFE), and of its main mutation (C282Y), has radically altered the way to diagnose this disease. The aim of this study was to assess the impact of the HFE gene discovery on the clinical presentation and epidemiology of HH.
  
  
  METHODS
  We studied our cohort of 415 patients homozygous for the C282Y allele and included in a phlebotomy program in a blood centre in western Brittany, France.
  
  
  RESULTS
  In this cohort, 56.9% of the patients were male and 21.9% began their phlebotomy program before the implementation of the genetic test. A significant decrease in the sex ratio was noticed following implementation of this DNA test, from 3.79 to 1.03 (p < 10(-5)), meaning that the proportion of diagnosed females relatives to males greatly increased. The profile of HH patients at diagnosis changed after the DNA test became available. Serum ferritin and iron values were lower and there was a reduced frequency of clinical signs displayed at diagnosis, particularly skin pigmentation (20.1 vs. 40.4%, OR = 0.37, p < 0.001) and hepatomegaly (11.0 vs. 22.7%, OR = 0.42, p = 0.006). In contrast, fatigue became a more common symptom at diagnosis (68.0 vs. 51.2%, OR = 2.03, p = 0.004).
  
  
  CONCLUSIONS
  This study highlights the importance of the HFE gene discovery, which has simplified the diagnosis of HH and modified its clinical presentation and epidemiology. This study precisely measures these changes. Enhanced diagnosis of HFE-related HH at an early stage and implementation of phlebotomy treatment are anticipated to maintain normal life expectancy for these patients.
authors.affiliation: INSERM U 613 Génétique Moléculaire et Génétique Epidémiologique, Brest, France. virginie.scotet@univ-brest.fr
authors.forename: Virginie
authors.initials: V
authors.lastname: Scotet
authors.forename: Gérald
authors.initials: G
authors.lastname: Le Gac
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Mérour
authors.forename: Anne-Yvonne
authors.initials: AY
authors.lastname: Mercier
authors.forename: Brigitte
authors.initials: B
authors.lastname: Chanu
authors.forename: Chandran
authors.initials: C
authors.lastname: Ka
authors.forename: Catherine
authors.initials: C
authors.lastname: Mura
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Nousbaum
authors.forename: Claude
authors.initials: C
authors.lastname: Férec
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution / Q000235:genetics; D015331:Cohort Studies; D003545:Cysteine / Q000235:genetics; D005260:Female; D005602:France; D005820:Genetic Testing; D005838:Genotype; D006432:Hemochromatosis / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques / Q000379:methods; D017720:Molecular Epidemiology / Q000379:methods / Q000639:trends*; D012744:Sex Ratio; D014443:Tyrosine / Q000235:genetics
chemical_list: C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D014443:Tyrosine; D003545:Cysteine