A targeted approach significantly increases the identification rate of patients with undiagnosed haemochromatosis

J Intern Med. 2003 Feb;253(2):217-24. doi: 10.1046/j.1365-2796.2003.01094.x.


Objective: To determine the optimal means of identifying patients with undiagnosed haemochromatosis.

Design: Case-control study where cases are defined by the presence of specific clinical diagnoses or symptoms.

Setting: Primary care patients were recruited from three Oxfordshire practices and secondary care patients were recruited from those patients attending specialist clinics in Amiens University Hospital.

Subjects: A total of 569 patients recruited via hospital clinics and 60 primary care patients (recruited from 4022 consultations) presenting with the following haemochromatosis associated conditions, diabetes, arthralgia/chronic fatigue, osteoporosis or arthropathy were studied. The control group, a total of 991 healthy volunteers, were recruited through a Health Appraisal Centre. Patients and controls were included in the study if they or their family members had not previously been diagnosed with hereditary haemochromatosis.

Main outcome measures: Serum ferritin concentration, transferrin saturation (Tsat) and presence of HFE mutations, C282Y and H63D. The check-up in controls consisted of a questionnaire, clinical examination, biochemical tests and screening for the presence of the C282Y and H63D mutations.

Results: Patient groups presenting with unstable diabetes or chronic fatigue and arthralgia together with a raised serum ferritin concentration showed an enrichment in the haemochromatosis-associated genotype HH/YY, odds ratio (OR) = 40.1, confidence interval (CI) = 8.0-202.1 and OR = 103, CI = 22.9-469.7, respectively.

Conclusion: Patients presenting to hospital clinics with haemochromatosis associated conditions should be screened biochemically for iron overload. Only those with a serum ferritin >300 microg L-1 or Tsat >40% should subsequently go on to be genotyped for HFE mutations. The patients at greatest risk of having undiagnosed haemochromatosis are those presenting with unstable diabetes, or fatigue and/or arthralgia in the absence of any other explanation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Case-Control Studies
  • Female
  • Ferritins / blood
  • Hemochromatosis / diagnosis*
  • Hemochromatosis / genetics
  • Hemochromatosis Protein
  • Heterozygote
  • Histocompatibility Antigens Class I / genetics*
  • Homozygote
  • Humans
  • Male
  • Membrane Proteins / genetics*
  • Middle Aged
  • Mutation / genetics*
  • Transferrin / analysis


  • HFE protein, human
  • Hemochromatosis Protein
  • Histocompatibility Antigens Class I
  • Membrane Proteins
  • Transferrin
  • Ferritins