Editing Alkaptonuria (section)

==History==
Alkaptonuria was one of the four diseases described by [[Archibald Edward Garrod]], as being the result of the accumulation of intermediates due to metabolic deficiencies. He linked [[ochronosis]] with the accumulation of alkaptans in 1902,<ref name=Zatkova2011/><ref>{{cite journal|author =Garrod AE|year=1902|title=The incidence of alkaptonuria: a study in clinical individuality|journal=Lancet|volume=2|pages=1616–20|doi=10.1016/S0140-6736(01)41972-6|pmid=8784780|issue=4137|pmc=2230159}} Reproduced in {{cite journal | author=Garrod AE| title=The incidence of alkaptonuria: a study in chemical individuality. 1902 classical article|journal=Yale Journal of Biology and Medicine | volume=75 | pages=221–31 |year=2002| pmid=12784973 | issue=4 | pmc=2588790}}</ref> and his views on the subject, including its mode of heritance, were summarized in a 1908 [[Croonian Lecture]] at the [[Royal College of Physicians]].<ref name=Zatkova2011/><ref>{{cite journal|author =Garrod AE|year=1908|title=The Croonian lectures on inborn errors of metabolism: lecture II: alkaptonuria|journal=Lancet|volume=2|issue= 4428|pages=73–79|doi=10.1016/s0140-6736(01)78041-5 |url=https://zenodo.org/record/1576909}}</ref><ref>{{cite book | author=Garrod AE | title=Inborn errors of metabolism | publisher=Oxford University Press | date=1909| ol=7116744M}}</ref> The genetics of it was also studied by [[William Bateson]] in 1902.<ref>{{cite book |last1=Kean |first1=Sam |title=The Violinist's thumb |pages=57–58}}</ref>

The defect was narrowed down to homogentisic acid oxidase deficiency in a study published in 1958.<ref name=Zatkova2011/><ref>{{cite journal |vauthors=La Du BN, Zannoni VG, Laster L, Seegmiller JE |title=The nature of the defect in tyrosine metabolism in alcaptonuria |journal=Journal of Biological Chemistry |volume=230 |issue=1 |pages=251–60 |date=1 January 1958 |doi=10.1016/S0021-9258(18)70560-7 |pmid=13502394 |doi-access=free }}</ref> The genetic basis was elucidated in 1996, when'' HGD'' mutations were demonstrated.<ref name=Zatkova2011/><ref>{{cite journal |vauthors=Fernández-Cañón JM, Granadino B, Beltrán-Valero de Bernabé D |title=The molecular basis of alkaptonuria |journal=Nature Genetics |volume=14 |issue=1 |pages=19–24 |year=1996 |pmid=8782815 |doi=10.1038/ng0996-19|s2cid=7809387 }}</ref>

A 1977 study showed that an ochronotic Egyptian [[mummy]] had probably suffered from alkaptonuria.<ref>{{cite journal |vauthors=Stenn FF, Milgram JW, Lee SL, Weigand RJ, Veis A |title=Biochemical identification of homogentisic acid pigment in an ochronotic egyptian mummy |journal=Science |volume=197 |issue=4303 |pages=566–68 |year=1977 |pmid=327549 |doi= 10.1126/science.327549|bibcode=1977Sci...197..566S }}</ref><ref>{{Cite journal  | last1 = Lee | first1 = SL. | last2 = Stenn | first2 = FF. | title = Characterization of mummy bone ochronotic pigment. | journal = JAMA | volume = 240 | issue = 2 | pages = 136–38 |date=Jul 1978  | pmid = 351220 |doi=10.1001/jama.1978.03290020058024}}</ref>