Editing Hereditary haemochromatosis (section)

== History ==
In 1847, [[Rudolf Virchow|Virchow]] described a golden brown granular pigment that was soluble in [[sulfuric acid]] and produced red ash on ignition.<ref name="978-0-521-59380-9">{{Cite book|editor-last1=Barton|editor-first1=James C.|url=https://books.google.com/books?id=kE6mmwm5d8UC&pg=PA3|title=Hemochromatosis: Genetics, Pathophysiology, Diagnosis and Treatment|editor-last2=Edwards|editor-first2=Corwin Q.|date=2000|publisher=Cambridge University Press|isbn=978-0-521-59380-9|language=en|access-date=2 July 2022|archive-date=2 July 2022|archive-url=https://web.archive.org/web/20220702135326/https://books.google.com/books?id=kE6mmwm5d8UC&pg=PA3|url-status=live}}</ref> The disease was first described in 1865 by [[Armand Trousseau]] in a report on diabetes in patients presenting with a bronze pigmentation of their skin.<ref name=Trousseau_1865>{{cite journal |vauthors=Trousseau A |title=Glycosurie, diabète sucré |journal=Clinique Médicale de l'Hôtel-Dieu de Paris |year=1865 |volume=2| pages=663–98}}</ref> Two years later, [[Perls Prussian blue|Perls]] developed the first practical method for the analysis of iron in tissue. Despite Trousseau not associating diabetes with iron accumulation, the recognition that infiltration of the pancreas with iron might disrupt endocrine function resulting in diabetes was made by [[Friedrich Daniel von Recklinghausen]] in 1890.<ref>{{cite journal |vauthors=von Recklinghausen FD |title=Hämochromatose |journal=Tageblatt der Naturforschenden Versammlung 1889 |year=1890 |page=324}}</ref><ref>{{Cite web|url=http://www.whonamedit.com/doctor.cfm/1174.html|title=Friedrich Daniel von Recklinghausen|website=www.whonamedit.com|access-date=24 March 2004|archive-date=16 November 2018|archive-url=https://web.archive.org/web/20181116053141/http://www.whonamedit.com/doctor.cfm/1174.html|url-status=live}}</ref> In 1935, English gerontologist Joseph Sheldon described the cases of haemochromatosis. He established this as the name of the disorder and his detailed monograph. Despite lacking the modern molecular techniques accessible today, he came to accurate conclusions that describe haemochromatosis disease as an inborn error of metabolism where this inherited disorder can increase the absorption of iron and thus cause tissue damage due to iron deposition. Moreover, he rejected theories that alcohol, drug, and other factors contribute to the disorder.<ref>{{Cite news|last=Sheldon|first=JH|date=1935|title=Haemochromatosis|work=London: Oxford University Press}}</ref><ref name="Bacon 2012 133–136">{{Cite journal |last=Bacon |first=Bruce R. |date=2012 |title=Hemochromatosis: Discovery of the HFE Gene |journal=Missouri Medicine |volume=109 |issue=2 |pages=133–136 |issn=0026-6620 |pmc=6181731 |pmid=22675794}}</ref><ref name="pmid12763361">{{Cite journal |last=Brissot |first=Pierre |date=June 2003 |title=The discovery of the new haemochromatosis gene: Feder JN, Gnirke A, Thomas W, Tsuchihashi Z, Ruddy DA, Basava A, et al. A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis [Nat Genet 1996;13:399–408] |url=https://www.journal-of-hepatology.eu/article/S0168-8278(03)00142-9/abstract |journal=Journal of Hepatology |language=en |volume=38 |issue=6 |pages=704–709 |doi=10.1016/S0168-8278(03)00142-9 |pmid=12763361 |issn=0168-8278 |doi-access=free |access-date=20 November 2021 |archive-date=8 March 2024 |archive-url=https://web.archive.org/web/20240308023347/https://www.journal-of-hepatology.eu/article/S0168-8278(03)00142-9/fulltext |url-status=live }}</ref>

The clinical case series from 1935 to 1955 indicated that haemochromatosis was more common than had been acknowledged.<ref name="978-0-521-59380-9"/> During the 1960s, MacDonald, a pathologist at Boston City Hospital, diverted attention away from the true cause of haemochromatosis. He believed that haemochromatosis was a nutritional condition because he observed many drunken patients of Irish ancestry.<ref>{{Cite book|last=MacDonald|first=RA|title=Hemochromatosis and Hemosiderosis|publisher=Springfield, IL: Charles C Thomas|year=1964}}</ref> During this period of time, other investigators reported additional evidence suggesting that a genetic factor could play a central role in the absorption of iron in people with haemochromatosis. However, alcohol consumption is known to increase the risk of liver injury in haemochromatosis. This finding is consistent with the concept that excess iron metabolism is a primary cause of haemochromatosis disease.<ref name="Bacon 2012 133–136"/>

Finally, in 1976, Marcel Simon and his collaborators confirmed that haemochromatosis is an autosomal recessive disorder that has a link to the human leukocyte antigen (HLA) region of the genome. It took 20 years for researchers at Mercator Genetics to effectively identify and clone the haemochromatosis genes using a positional cloning approach.<ref>{{Cite journal|vauthors=Simon M, Bourel M, Fauchet R, Genetet B |title=Association of HLA-A3 and HLA-B14 antigens with idiopathic haemochromatosis |journal=Gut |year=1976 |volume=17 |issue=5 |pages=332–334 |doi=10.1136/gut.17.5.332 |pmid=1278715 |pmc=1411133}}</ref>

In 1996, Feder et al. identified HFE, which is a major histocompatibility complex (MHC) gene. They found that 83% of patients have homozygosity for a [[missense mutation]] (C282Y) in the HFE gene.<ref name="pmid8696333"/><ref name="Bacon 2012 133–136"/><ref name="pmid12763361"/> Finally, several groups reported their findings in a series of patients with haemmochromatosis where they discovered the existence of the C282Y mutation in about 85-90% of the cases. The discovery has led to improved clinical medicine and liver disease evaluation.<ref name="Bacon 2012 133–136"/>