title: Improved detection of hereditary haemochromatosis.
abstract: OBJECTIVE
  There is high prevalence of hereditary haemochromatosis (HH) in North European populations, yet the diagnosis is often delayed or missed in primary care. Primary care physicians frequently request serum ferritin (SF) estimation but appear uncertain as how to investigate patients with raised SF values. Our aim was to develop a laboratory algorithm with high predictive value for the diagnosis of HH in patients from primary care with raised SF values.
  
  
  METHODS
  Transferrin saturation (Tsat) was measured on SF samples sent from primary care; 1657 male and 2077 female patients age ≥ 30 years with SF ≥ 200 μg/L. HFE genotyping was performed on all 878 male and 867 female patients with Tsat >30%.
  
  
  RESULTS
  This study identified 402 (206 men; 196 women) C282Y carriers and 132 (58 men; 74 women) C282Y homozygotes. Optimal limits for combined SF and Tsat values for HH recognition were established. The detection rate for homozygous C282Y HH for male patients with both SF ≥ 300 μg/L and Tsat >50% was 18.8% (52/272) and 16.3% (68/415) for female patients with both SF ≥ 200 μg/L and Tsat >40%.
  
  
  CONCLUSIONS
  The large number of SF requests received from primary care should be used as a resource to improve the diagnosis of HH in areas of high prevalence.
authors.affiliation: Department of Haematology, West Glasgow Hospitals University NHS Trust, Glasgow, UK.
authors.forename: Catherine
authors.initials: C
authors.lastname: Ogilvie
authors.affiliation: Department of Biochemistry, Glasgow Royal Infirmary, Glasgow, UK.
authors.forename: Dairena
authors.initials: D
authors.lastname: Gaffney
authors.affiliation: Robertson Centre for Biostatistics, University of Glasgow, Glasgow, UK.
authors.forename: Heather
authors.initials: H
authors.lastname: Murray
authors.affiliation: Department of Clinical Biochemistry, Royal Alexandra Hospital, Paisley, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Kerry
authors.affiliation: Robertson Centre for Biostatistics, University of Glasgow, Glasgow, UK.
authors.forename: Caroline
authors.initials: C
authors.lastname: Haig
authors.affiliation: Department of Biochemistry, Glasgow Royal Infirmary, Glasgow, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Spooner
authors.affiliation: Department of Haematology, West Glasgow Hospitals University NHS Trust, Glasgow, UK.
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Fitzsimons
mesh_terms: D000328:Adult; D000368:Aged; D000465:Algorithms; D015415:Biomarkers / Q000097:blood; D019091:Critical Pathways; D004252:DNA Mutational Analysis; D005260:Female; D005293:Ferritins / Q000097:blood; D020022:Genetic Predisposition to Disease; D006432:Hemochromatosis / Q000175:diagnosis* / Q000235:genetics; D000071020:Hemochromatosis Protein; D040941:Heredity; D006579:Heterozygote; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D006720:Homozygote; D006801:Humans; D007755:Laboratories, Hospital; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D011237:Predictive Value of Tests; D011320:Primary Health Care; D012017:Referral and Consultation; D014168:Transferrin / Q000032:analysis; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D014168:Transferrin; D005293:Ferritins
keywords: Haemochromatosis; IRON; LABORATORY TESTS