Skip to main content

Hereditary Haemochromatosis

  • Chapter
  • First Online:
Liver Disease in Clinical Practice

Part of the book series: In Clinical Practice ((ICP))

  • 524 Accesses

Abstract

2021 marked the 25th anniversary of the discovery of the HFE gene, a major genetic breakthrough which revolutionised the understanding and diagnosis of hereditary haemochromatosis (HH). The original description of the condition ‘bronze diabetes’ is now rare with earlier presentations being the norm due to increased awareness and easier diagnosis. Importantly, a diagnosis of HH can be made quite readily now in primary care via HFE genotyping. Liver biopsy is reserved for fibrosis staging although non-invasive methods such as transient elastography are becoming complementary. Cirrhosis impacts on survival, and certain manifestations, such as arthritis, do not respond well to phlebotomy; the latter is a source of long-term morbidity in many patients, hence the need to diagnose the condition early. Asymptomatic HFE positive individuals may not necessarily benefit from immediate therapeutic venesection, e.g. pre-menopausal females with normal ferritin, elderly patients and compound heterozygotes. Importantly, the National Blood Service will consider treated HH individuals for maintenance phlebotomy, which provides benefit to other patients. Clinicians require a low index of suspicion for diagnosis and should implement cascade screening once a case is identified. The identification of HFE spawned a new era of molecular genetic research and a number of rarer inherited forms of iron overload have since been recognised; advanced genetic testing is now more readily available for clinicians and novel molecular therapies are in development.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 37.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 37.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  1. Niederau C, Fischer R, Sonnenberg A, et al. Survival and causes of death in cirrhotic and in noncirrhotic patients with primary hemochromatosis. N Engl J Med. 1985;313:1256–62.

    Article  CAS  PubMed  Google Scholar 

  2. 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;13:399–408.

    Article  CAS  PubMed  Google Scholar 

  3. Merryweather-Clarke AT, Pointon JJ, Shearman JD, Robson KJ. Global prevalence of putative haemochromatosis mutations. J Med Genet. 1997;34:275–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Pilling LC, Tamosauskaite J, Jones G, et al. Common conditions associated with hereditary haemochromatosis genetic variants: cohort study in UK Biobank. BMJ. 2019;364:k5222.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Buch S, Sharma A, Ryan E, et al. Variants in PCSK7, PNPLA3 and TM6SF2 are risk factors for the development of cirrhosis in hereditary haemochromatosis. Aliment Pharmacol Ther. 2021;53(7):830–43.

    CAS  PubMed  Google Scholar 

  6. EASL Clinical Practice Guidelines on haemochromatosis. European association for the study of the liver. J Hepatol. 2022;77:479–502.

    Google Scholar 

  7. Guyader D, Jazquelinet C, Moirand R, et al. Noninvasive prediction of fibrosis in C282Y homozygous hemochromatosis. Gastroenterology. 1998;115:929–36.

    Article  CAS  PubMed  Google Scholar 

  8. Legros L, Bardou-Jacquet E, Latournerie M, et al. Non-invasive assessment of liver fibrosis in C282Y homoyzgous HFE hemochromatosis. Liver Int. 2015;35:1731–8.

    Article  CAS  PubMed  Google Scholar 

  9. Bardo-Jacquet E, Laine F, Guggenbuhi P, et al. Worse outcomes of patients with HFE hemochromatosis with persistent increases in transferrin saturation during maintenance therapy. Clin Gastroenterol Hepatol. 2017;15:1620–7.

    Article  Google Scholar 

  10. Fitzsimons EJ, Cullis JO, Thomas DW, et al. Diagnosis and therapy of genetic haemochromatosis (review and 2017 update). Br J Haematol. 2018;181:293–303.

    Article  PubMed  Google Scholar 

  11. Falize L, Guillygomarc'h A, Perrin M, et al. Reversibility of hepatic fibrosis in treated genetic hemochromatosis: a study of 36 cases. Hepatology. 2006;44:472–7.

    Article  PubMed  Google Scholar 

  12. Gurrin LC, Osborne NJ, Constantine CC, et al. The natural history of serum iron indices for HFE C282Y homozygosity associated with hereditary hemochromatosis. Gastroenterology. 2008;135:1945–52.

    Article  CAS  PubMed  Google Scholar 

  13. Phatak P, Brissot P, Wurster M, et al. A phase 1/2, dose-escalation trial of deferasirox for the treatment of iron overload in HFE-related hereditary hemochromatosis. Hepatology. 2010;52:1671–779.

    Article  CAS  PubMed  Google Scholar 

  14. Griffiths WJH, Besser M, Bowden DJ, Kelly DA. Juvenile haemochromatosis. Lancet Child Adolesc Health. 2021;5:524–30.

    Google Scholar 

  15. Bhuva M, Sen S, Elsey T, et al. Sequence analysis of exon 1 of the ferritin light chain (FTL) gene can reveal the rare disorder ‘hereditary hyperferritinaemia without cataracts’. Br J Haematol. 2019;184:1037–40.

    Article  PubMed  Google Scholar 

  16. Nemeth E, Tuttle MS, Powelson J, et al. Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science. 2004;306:2090–3.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to William J. H. Griffiths .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2022 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Griffiths, W.J.H. (2022). Hereditary Haemochromatosis. In: Cross, T. (eds) Liver Disease in Clinical Practice. In Clinical Practice. Springer, Cham. https://doi.org/10.1007/978-3-031-10012-3_12

Download citation

  • DOI: https://doi.org/10.1007/978-3-031-10012-3_12

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-031-10011-6

  • Online ISBN: 978-3-031-10012-3

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics