title: Using iron studies to predict HFE mutations in New Zealand: implications for laboratory testing.
abstract: BACKGROUND
  The diagnosis of hereditary haemochromatosis (HH) is not straightforward because symptoms are often absent or non-specific. Biochemical markers of iron-overloading may be affected by other conditions.
  
  
  OBJECTIVE
  To measure the correlation between iron studies and HFE genotype to inform evidence-based recommendations for laboratory testing in New Zealand.
  
  
  METHODS
  Results from 2388 patients genotyped for C282Y, H63D and S65C in Wellington, New Zealand from 2007 to 2013 were compared with their biochemical phenotype as quantified by serum ferritin (SF), transferrin saturation (TS), serum iron (SI) and serum transferrin (ST). The predictive power of these markers was evaluated by receiver operator characteristic (ROC) curve analysis, and if a statistically significant association for a variable was seen, sensitivity, specificity and predictive values were calculated.
  
  
  RESULTS
  Test ordering patterns showed that 62% of HFE genotyping tests were ordered because of an elevated SF alone and only 11% of these had a C-reactive protein test to rule out an acute phase reaction. The association between SF and significant HFE genotypes SF was low. However, TS values ≥45% predicted HH mutations with the highest sensitivity and specificity. A SF of >1000 µg/L was found in one at-risk patient (C282Y homozygote) who had a TS <45%.
  
  
  CONCLUSIONS
  Our analysis highlights the need for clear guidelines for investigation of hyperferritinaemia and HH in New Zealand. Using our findings, we developed an evidence-based laboratory testing algorithm based on a TS ≥45%, a SF ≥1000 µg/L and/or a family history of HH which identified all C282Y homozygotes in this study.
authors.affiliation: Haematology Department, Wellington Southern Community Laboratories, Wellington, New Zealand.
authors.forename: Rebecca
authors.initials: R
authors.lastname: O'Toole
authors.affiliation: Haematology Department, Wellington Southern Community Laboratories, Wellington, New Zealand.|Capital and Coast District Health Board, Laboratory Services, Wellington Hospital, Wellington, New Zealand.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Romeril
authors.affiliation: College of Health, Massey University, Wellington, New Zealand.
authors.forename: Collette
authors.initials: C
authors.lastname: Bromhead
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019411:Clinical Laboratory Techniques; D004252:DNA Mutational Analysis; D005260:Female; D005293:Ferritins / Q000097:blood; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005820:Genetic Testing / Q000379:methods*; D005838:Genotype; D006432:Hemochromatosis / Q000097:blood* / Q000453:epidemiology / Q000235:genetics; D000071020:Hemochromatosis Protein / Q000097:blood*; D006801:Humans; D007501:Iron / Q000097:blood*; D019190:Iron Overload; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009520:New Zealand / Q000453:epidemiology; D011237:Predictive Value of Tests; D015995:Prevalence; D014168:Transferrin / Q000378:metabolism; D055815:Young Adult
chemical_list: C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D008565:Membrane Proteins; D014168:Transferrin; D005293:Ferritins; D007501:Iron
keywords: 
  
  HFE
   gene; hereditary haemochromatosis; hyperferritinaemia; iron; transferrin