Irish Journal of Medical Science

, Volume 175, Issue 1, pp 32–36

The Celtic coincidence — the frequency and clinical characterisation of hereditary haemochromatosis in patients with coeliac disease

  • J. Leyden
  • B. Kelleher
  • E. Ryan
  • S. Barrett
  • J. C. O’Keane
  • J. Crowe
Original Paper

Abstract

Background

Hereditary Haemochromatosis (HH) and Coeliac disease (CD) are common disorders in Northern European populations, particularly the Irish population.

Aims

To investigate whether there was increased frequency of the two commonHFE gene mutations, C282Y and H63D, associated with HH amongst a cohort of CD patients, and to determine the penetrance of the HH associated genotypes in this cohort.

Methods

HFE genotypes of a cohort of CD patients were determined using standard PCR techniques.HFE allele frequencies were compared to those of a previously reported, ethnically similar, cohort of 800 neonates, using Fishers exact test. Patients with HH-associated genotypes were subsequently evaluated.

Results

The C282Y and H63D allele frequencies, 24/222 (11%) and 28/222 (13%) respectively, in the CD patients were similar to those of the neonatal group, 171/1600 (11%) and 242/1600 (15%). Eight patients had HH-associated genotypes, of which two demonstrated biochemical evidence of iron overload.

Conclusion

TheHFE mutations associated with Hereditary Haemochromatosis are not more common in Irish CD patients.

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References

  1. 1.
    Feder JN, Gnirke A, Thomas W, et al. A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis.Nat Genet 1996; 13(4): 399–408.CrossRefPubMedGoogle Scholar
  2. 2.
    Pietrangelo A. Hereditary Hemochromatosis — a new look at an old disease.N Engl J Med 2004;350 (23): 2383–97CrossRefPubMedGoogle Scholar
  3. 3.
    Adams P, Brissot P, Powell LW. EASL International Consensus Conference on Haemochromatosis. J Hepatol 2000; 33(3): 485–504.CrossRefPubMedGoogle Scholar
  4. 4.
    Ryan E, O’Keane C, Crowe J. Hemochromatosis in Ireland and HFE.Blood Celts Mol Dis 1998; 24(4): 428–432.CrossRefGoogle Scholar
  5. 5.
    Byrnes V, Ryan E, Barrett S, Kenny P, Mayne P, Crowe J. Genetic hemochromatosis, a Celtic disease: is it now time for population screening?Genet Test 2001; 5(2): 127–130.CrossRefPubMedGoogle Scholar
  6. 6.
    Olynyk JK, Cullen DJ, Aquilia S, Rossi E, Summerville L, Powell LW. A population-based study of the clinical expression of the hemochromatosis gene. N Engl J Med 1999; 341(10)718–724.CrossRefPubMedGoogle Scholar
  7. 7.
    Burt MJ, George PM, Upton JD, et al. The significance of haemochromatosis gene mutations in the general population: implications for screening. Gut 1998; 43(6): 830–836.PubMedCrossRefGoogle Scholar
  8. 8.
    Merryweather-Clarke AT, Pointon JJ, Jouanolle AM, Rochette J, Robson KJ. Geography of HFE C282Y and H63D mutations.Genet Test 2000; 4(2): 183–198.CrossRefPubMedGoogle Scholar
  9. 9.
    Bomford A. Genetics of haemochromatosis.Lancet 2002; 360(9346): 1673–1681.CrossRefPubMedGoogle Scholar
  10. 10.
    Ryan E, Byrnes V, Coughlan B, et al. Underdiagnosis of hereditary haemochromatosis: lack of presentation or penetration?Gut 2002; 51(1): 108–112.CrossRefPubMedGoogle Scholar
  11. 11.
    Asberg A, Hveem K, Thorstensen K, et al. Screening for hemochromatosis: high prevalence and low morbidity in an unselected population of 65,238 persons.Scand J Gastroenterol 2001; 36(10): 1108–1115.CrossRefPubMedGoogle Scholar
  12. 12.
    Beutler E, Felitti VJ, Koziol JA, Ho NJ, Gelbart T. Penetrance of 845G → A (C282Y) HFE hereditary haemochromatosis mutation in the USA.Lancet 2002; 359(9302): 211–218.CrossRefPubMedGoogle Scholar
  13. 13.
    Jackson HA, Carter K, Darke C, et al. HFE mutations, iron deficiency and overload in 10,500 blood donors.Br J Haematol 2001; 114(2): 474–484.CrossRefPubMedGoogle Scholar
  14. 14.
    Gochee PA, Powell LW, Cullen DJ, Du SD, Rossi E, Olynyk JK. A population-based study of the biochemical and clinical expression of the H63D hemochromatosis mutation.Gastroenterology 2002; 122(3): 646–651.CrossRefPubMedGoogle Scholar
  15. 15.
    Farrell RJ, Kelly CP. Celiac sprue.N Engl J Med 2002; 346(3): 180–188.CrossRefPubMedGoogle Scholar
  16. 16.
    Mylotte M, Egan-Mitchell B, McCarthy CF, McNicholl B. Coeliac disease in the West of Ireland.Br Med J 1973; 3(5878): 498–499.CrossRefPubMedGoogle Scholar
  17. 17.
    McLoughlin R, Sebastian SS, Qasim A, et al. Coeliac disease in Europe.Aliment Pharmacol Ther 2003; 18 Suppl 3: 45–48.CrossRefPubMedGoogle Scholar
  18. 18.
    Johnston SD, Watson RG, McMillan SA, Sloan J, Love AH. Prevalence of coeliac disease in Northern Ireland.Lancet 1997; 350(9088): 1370.CrossRefPubMedGoogle Scholar
  19. 19.
    Singhal A, Moreea S, Reynolds PD, Bzeizi KI. Coeliac disease and hereditary haemochromatosis: association and implications.EurJ Gastroenterol Hepatol 2004; 16(2): 235–237.CrossRefGoogle Scholar
  20. 20.
    Butterworth JR, Cooper BT, Rosenberg WM, et al. The role of hemochromatosis susceptibility gene mutations in protecting against iron deficiency in celiac disease.Gastroenterology 2002; 123(2): 444–449.CrossRefPubMedGoogle Scholar
  21. 21.
    Heneghan MA, Feeley KM, Stevens FM, Little MP, McCarthy CF. Precipitation of iron overload and hereditary hemochromatosis after successful treatment of celiac disease.Am J Gastroenterol 2000; 95(1): 298–300.CrossRefPubMedGoogle Scholar
  22. 22.
    Scheuer PJ, Williams R, Muir AR. Hepatic pathology in relatives of patients with haemochromatosis.J Pathol Bacteriol 1962; 84: 53–64.CrossRefPubMedGoogle Scholar
  23. 23.
    Barisani D, Ceroni S, Del Bianco S, Meneveri R, Bardella MT. Hemochromatosis gene mutations and iron metabolism in celiac disease.Haematologica 2004; 89(11): 1299–1305.PubMedGoogle Scholar
  24. 24.
    Beutler E, Felitti V, Gelbart T, Waalen J. Haematological effects of the C282Y HFE mutation in homozygous and heterozygous states among subjects of northern and southern European ancestry.Br J Haematol 2003; 120(5): 887–893.CrossRefPubMedGoogle Scholar
  25. 25.
    Burke W, Thomson E, Khoury MJ, et al. Hereditary hemochromatosis: gene discovery and its implications for population-based screenmg.JAMA 1998; 280(2): 172–178.CrossRefPubMedGoogle Scholar

Copyright information

© Springer 2006

Authors and Affiliations

  • J. Leyden
    • 2
  • B. Kelleher
    • 2
  • E. Ryan
    • 2
  • S. Barrett
    • 2
  • J. C. O’Keane
    • 1
    • 2
  • J. Crowe
    • 2
  1. 1.Centre for Liver DiseaseMater Misericordiae University HospitalDublin
  2. 2.Dept of PathologyMater Misericordiae University HospitalDublin
  3. 3.Centre for Liver DiseaseMater Misericordiae University Hospital, University College DublinDublin 7

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