Hereditary haemochromatosis

This article is about hereditary haemochromatosis (HHC) associated with the HFE gene. For other causes of haemochromatosis, see Iron overload.

Haemochromatosis type 1
Other namesHFE hereditary haemochromatosis[1] HFE-related hereditary haemochromatosis[2]
Iron accumulation demonstrated by Prussian blue staining in a patient with homozygous genetic haemochromatosis (microscopy, 10x magnified): Parts of normal pink tissue are scarcely present.
SpecialtyEndocrinology, hepatology Edit this on Wikidata
Differential diagnosis

Hereditary haemochromatosis type 1 (HFE-related haemochromatosis)[3] is a genetic disorder characterized by excessive intestinal absorption of dietary iron, resulting in a pathological increase in total body iron stores.[4] Humans, like most animals, have no mechanism to regulate excess iron, simply losing a limited amount through various means like sweating or menstruating.[5][6][7]

Excess iron accumulates in tissues and organs, disrupting their normal function. The most susceptible organs include the liver, heart, pancreas, skin, joints, gonads, thyroid and pituitary gland; patients can present with cirrhosis, polyarthropathy, hypogonadism, heart failure, or diabetes.[8]

There are five types of hereditary hemochromatosis: type 1, 2 (2A, 2B), 3, 4[9] and 5,[10] all caused by mutated genes. Hereditary hemochromatosis type 1 is the most frequent, and uniquely related to the HFE gene. It is most common among those of Northern European ancestry, in particular those of Celtic descent.[11]

The disease follows an autosomal recessive pattern of inheritance, meaning that an individual must inherit two copies of the mutated gene involved in each cell to develop the condition.[12] In most cases, when a person has this autosomal recessive condition, their parents act as carriers. Carriers possess one copy of the mutated gene but do not manifest any signs or symptoms associated with the disease, and are referred to as carriers. The unaffected carrier parents play an integral role in transmitting one copy of the mutated gene to their child, who ultimately develops the disease. However, carriers may experience iron overload themselves at a later stage if certain factors come into play. Still, in most cases, they remain asymptomatic throughout their lives unless other genetic or environmental factors contribute to excessive iron accumulation within their bodies.[12]

  1. ^ Allen KJ, Gurrin LC, Constantine CC, et al. (January 2008). "Iron-overload-related disease in HFE hereditary hemochromatosis" (PDF). N. Engl. J. Med. 358 (3): 221–30. doi:10.1056/NEJMoa073286. PMID 18199861. Archived (PDF) from the original on 28 August 2021. Retrieved 10 June 2019.
  2. ^ Jacobs EM, Verbeek AL, Kreeftenberg HG, et al. (December 2007). "Changing aspects of HFE-related hereditary haemochromatosis and endeavours to early diagnosis". Neth J Med. 65 (11): 419–24. PMID 18079564. Archived from the original on 6 May 2021.
  3. ^ Franchini M (March 2006). "Hereditary iron overload: update on pathophysiology, diagnosis, and treatment". Am. J. Hematol. 81 (3): 202–9. doi:10.1002/ajh.20493. PMID 16493621. S2CID 40950367.
  4. ^ St John A (June 2011). "Testing for HFE-related haemochromatosis" (PDF). Australian Prescriber. 34 (34): 73–6. doi:10.18773/austprescr.2011.046. Retrieved 3 June 2011.[permanent dead link‍]
  5. ^ Janet RH (June 2009). "Body iron excretion by healthy men and women". The American Journal of Clinical Nutrition. 89 (6): 1792–1798. doi:10.3945/ajcn.2009.27439. PMID 19386738.
  6. ^ "The interaction of iron and erythropoietin". sickle.bwh.harvard.edu. Archived from the original on 13 December 2022. Retrieved 25 July 2022.
  7. ^ Ofojekwu MJ, Nnanna OU, Okolie CE, Odewumi LA, Isiguzoro IO, Lugos MD (2013). "Hemoglobin and Serum Iron Concentrations in Menstruating Nulliparous Women in Jos, Nigeria". Laboratory Medicine. 44 (2): 121–124. doi:10.1309/LMM7A0F0QBXEYSSI. S2CID 73154256.
  8. ^ "Hereditary Hemochromatosis". www.cdc.gov. Centers for Disease Control and Prevention. Archived from the original on 2 June 2021.
  9. ^ Cite error: The named reference YY was invoked but never defined (see the help page).
  10. ^ "FTH1-related iron overload - About the Disease". Genetic and Rare Diseases Information Center. Archived from the original on 13 December 2022. Retrieved 24 May 2021.
  11. ^ Messmer J (16 March 2005). "The Medical Minute: Hemochromatosis -- the Celtic curse". news.psu.edu. Penn State University. Archived from the original on 17 December 2023.
  12. ^ a b Reference GH. "Hereditary hemochromatosis". Genetics Home Reference. Archived from the original on 16 August 2019. Retrieved 22 July 2019.