17β-Hydroxysteroid dehydrogenase III deficiency

Rare autosomal recessive disorder causing impaired masculinisation 17β-Hydroxysteroid dehydrogenase III deficiency 17 alpha ketosteroid reductase deficiency of testis,17-beta hydroxysteroid dehydrogenase 3 deficiency Genetic and Rare Diseases Information Center (GARD) – an NCATS Program https://rarediseases.info.nih.gov/diseases/5659/index dead https://web.archive.org/web/20190730105234/https://rarediseases.info.nih.gov/diseases/5659/index 30 July 2019 30 July 2019 rarediseases.info.nih.gov 46,XY difference of sex development due to 17-beta-hydroxysteroid dehydrogenase 3 deficiency, 17-ketoreductase deficiency, 17-ketosteroidreductase deficiency. Image:Test biosynth 17BHSD3.jpg Biochemical effects of 17β-hydroxysteroid deficiency-3 in testosterone biosynthesis. Typically levels of androstenedione are significantly increased, whilst testosterone levels are decreased, leading to male undervirilization. Hypothyroidism, Cryptorchidism17-beta hydroxysteroid dehydrogenase 3 deficiency Genetic and Rare Diseases Information Center (GARD) – an NCATS Program https://rarediseases.info.nih.gov/diseases/5659/17-beta-hydroxysteroid-dehydrogenase-3-deficiency dead https://web.archive.org/web/20190505124532/https://rarediseases.info.nih.gov/diseases/5659/17-beta-hydroxysteroid-dehydrogenase-3-deficiency 2019-05-05 2017-03-11 rarediseases.info.nih.gov en Mutations found in the 17β-HSD III gene Genetic testing Gonads should be monitored (possible malignancy) 17β-Hydroxysteroid dehydrogenase III deficiency is a rare autosomal recessive disorder of sexual development condition that is a cause of 46,XY disorder of sex development (46,XY DSD). The impaired testosterone biosynthesis by 17β-hydroxysteroid dehydrogenase III (17β-HSD III),Reference Genetics Home 17-beta hydroxysteroid dehydrogenase 3 deficiency https://medlineplus.gov/genetics/condition/17-beta-hydroxysteroid-dehydrogenase-3-deficiency/ live https://web.archive.org/web/20190505124530/https://ghr.nlm.nih.gov/condition/17-beta-hydroxysteroid-dehydrogenase-3-deficiency 2019-05-05 2017-03-11 Genetics Home Reference enOMIM Entry - # 264300 - 17-BETA HYDROXYSTEROID DEHYDROGENASE III DEFICIENCY https://omim.org/entry/264300 live https://web.archive.org/web/20190505124530/https://omim.org/entry/264300 2019-05-05 2017-03-11 omim.org en-us presents as atypical genitalia in affected males.Mendonca Berenice B. Gomes Nathalia Lisboa Costa Elaine M.F. Inacio Marlene Martin Regina M. Nishi Mirian Y. Carvalho Filomena Marino Tibor Francisco Denes Domenice Sorahia January 2017 46,XY disorder of sex development (DSD) due to 17β-hydroxysteroid dehydrogenase type 3 deficiency The Journal of Steroid Biochemistry and Molecular Biology 165 Pt A 79–85 10.1016/j.jsbmb.2016.05.002 27163392 25083887 free Signs and symptoms 17-β-Hydroxysteroid dehydrogenase III deficiency is a cause of 46,XY disorder of sex development (46,XY DSD) that presents in males with variable effects on genitalia which can be complete or predominantly female with a blind vaginal pouch. Testes are often found in the inguinal canal or in a bifid scrotum. Wolffian derivatives including the epididymides, vas deferens, seminal vesicles, and ejaculatory ducts are present.The autosomal recessive deficiency arises are a result of homozygous or compound heterozygous mutations in HSD17B3 gene which encodes the 17β-hydroxysteroid dehydrogenase III enzyme, impairing of the conversion of 17-keto into 17-hydroxysteroids. The enzyme is involved in the last phase of steroidogenesis and is responsible for the conversion of androstenedione to testosterone and estrone to estradiol. Virilization of affected males still occurs at puberty. Genetics 17β-Hydroxysteroid dehydrogenase III deficiency is caused by mutations found in the 17β-HSD III (17BHSD3) gene.17β-HSD III deficiency is an autosomal recessive disorder.Reference Genetics Home HSD17B3 gene https://medlineplus.gov/genetics/gene/hsd17b3/ live https://web.archive.org/web/20190505124530/https://ghr.nlm.nih.gov/gene/HSD17B3#conditions 5 May 2019 11 March 2017 Genetics Home Reference enRESERVED INSERM US14 -- ALL RIGHTS Orphanet: 46,XY disorder of sex development due to 17 beta hydroxysteroid dehydrogenase 3 deficiency http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Expert=752&lng=EN live https://web.archive.org/web/20171128093453/http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=752 2017-11-28 2017-03-12 www.orpha.net en Mechanism thumb|class=bg-transparent|Androstenedione Androstenedione is produced in the testis, as well as the adrenal cortex. Androstenedione is created from dehydroepiandrosterone (DHEA) or 17-hydroxyprogesterone.Pubchem androstenedione C19H26O2 - PubChem https://pubchem.ncbi.nlm.nih.gov/compound/androstenedione#section=Top live https://web.archive.org/web/20190505124536/https://pubchem.ncbi.nlm.nih.gov/compound/androstenedione#section=Top 2019-05-05 2017-03-17 pubchem.ncbi.nlm.nih.gov en A deficiency in the HSD17B3 gene is characterized biochemically by decreased levels of testosterone which results in the insufficient formation of dihydrotestosterone during fetal development. During the expected time of puberty, there is an increase in plasma luteinizing hormone and, consequently, in the testicular secretion of androstenedione. This leads to a clinically important higher ratio of androstenedione to testosterone.HSD17B3 hydroxysteroid 17-beta dehydrogenase 3 [Homo sapiens (human)] - Gene - NCBI https://www.ncbi.nlm.nih.gov/gene/3293 live https://web.archive.org/web/20181215101940/https://www.ncbi.nlm.nih.gov/gene/3293 2018-12-15 2017-03-13 www.ncbi.nlm.nih.govOMIM Entry - * 605573 - 17-BETA HYDROXYSTEROID DEHYDROGENASE III; HSD17B3 http://omim.org/entry/605573 live https://web.archive.org/web/20190505124530/http://omim.org/entry/605573 2019-05-05 2017-03-13 omim.org en-us Diagnosis In terms of the diagnosis of 17β-hydroxysteroid dehydrogenase III deficiency the following should be taken into account:Testosterone 17-beta-dehydrogenase deficiency - Conditions - GTR - NCBI https://www.ncbi.nlm.nih.gov/gtr/conditions/C0268296/ live https://web.archive.org/web/20190605034202/https://www.ncbi.nlm.nih.gov/gtr/conditions/C0268296/ 2019-06-05 2017-03-17 www.ncbi.nlm.nih.gov en Increased androstenedione:testosterone ratio Thyroid dyshormonogenesis Genetic testing Management Intersex medical interventions The 2006 Consensus statement on the management of intersex disorders states that individuals with 17β-hydroxysteroid dehydrogenase III deficiency have an intermediate risk of germ cell malignancy, at 28%, recommending that gonads be monitored.Lee P. A. Houk C. P. Ahmed S. F. Hughes I. A. 2006 Consensus statement on management of intersex disorders Pediatrics 118 2 e488–500 10.1542/peds.2006-0738 2082839 16882788 A 2010 review put the risk of germ cell tumors at 17%.Pleskacova J. Hersmus R. Oosterhuis J.W. Setyawati B.A. Faradz S.M. Cools M. Wolffenbuttel K.P. Lebl J. Drop S.L. Looijenga L.H. 2010 Tumor Risk in Disorders of Sex Development Sexual Development 4 4–5 259–269 10.1159/000314536 1661-5433 20558977 1847011The management of 17β-hydroxysteroid dehydrogenase III deficiency can consist, according to one source, of the elimination of gonads prior to puberty, in turn halting masculinization. Hewitt and Warne state that, children with 17β-hydroxysteroid dehydrogenase III deficiency who are raised as girls often later identify as male, describing a "well known, spontaneous change of gender identity from female to male" that "occurs after the onset of puberty."Hewitt Jacqueline K. Warne Garry L. February 2009 Management of disorders of sex development Pediatric Health 3 1 51–65 10.2217/17455111.3.1.51 1745-5111 A 2005 systematic review of gender role change identified the rate of gender role change as occurring in 39–64% of individuals with 17β-hydroxysteroid dehydrogenase III deficiency raised as girls.Cohen-Kettenis Peggy T. August 2005 Gender Change in 46,XY Persons with 5α-Reductase-2 Deficiency and 17β-Hydroxysteroid Dehydrogenase-3 Deficiency Archives of Sexual Behavior 34 4 399–410 10.1007/s10508-005-4339-4 0004-0002 16010463 146495456 Society and culture Modification of children's sex characteristics to meet social and medical norms is strongly contested, with numerous statements by civil society organizations and human rights institutions condemning such interventions, including describing them as harmful practices.Office of the High Commissioner for Human Rights Office of the High Commissioner for Human Rights October 24, 2016 Intersex Awareness Day – Wednesday 26 October. End violence and harmful medical practices on intersex children and adults, UN and regional experts urge http://www.ohchr.org/EN/NewsEvents/Pages/DisplayNews.aspx?NewsID=20739&LangID=E live https://web.archive.org/web/20161121185256/http://ohchr.org/EN/NewsEvents/Pages/DisplayNews.aspx?NewsID=20739&LangID=E November 21, 2016 March 19, 2017Report of the UN Special Rapporteur on Torture https://web.archive.org/web/20160824161117/http://www.ohchr.org/Documents/HRBodies/HRCouncil/RegularSession/Session22/A.HRC.22.53_English.pdf 2016-08-24 , Office of the UN High Commissioner for Human Rights, February 2013.Council of Europe Human rights and intersex people, Issue Paper April 2015 https://wcd.coe.int/ViewDoc.jsp?Ref=CommDH/IssuePaper(2015)1&Language=lanEnglish&Ver=original 2017-03-19 https://web.archive.org/web/20160106203349/https://wcd.coe.int/ViewDoc.jsp?Ref=CommDH%2FIssuePaper%282015%291&Language=lanEnglish&Ver=original 2016-01-06 live Commissioner for Human Rights Council of Europe Commissioner for Human Rights The case of Carla Intersex rights in Australia A 2016 case before the Family Court of AustraliaFamCA 7 2016 Re: Carla (Medical procedure) auto 20 January 2016. was widely reported in national,Overington Caroline Caroline Overington December 7, 2016 Family Court backs parents on removal of gonads from intersex child http://www.theaustralian.com.au/news/health-science/family-court-backs-parents-on-removal-of-gonads-from-intersex-child/news-story/60df936c557e2e21707eb198f1300276 live https://web.archive.org/web/20211204014823/https://insight.adsrvr.org/track/up?adv=vrges6n&ref=https%3A%2F%2Fwww.theaustralian.com.au%2Fsubscribe%2Fnews%2F1%2F%3FsourceCode%3DTAWEB_WRE170_a%26dest%3Dhttps%253A%252F%252Fwww.theaustralian.com.au%252Fnews%252Fhealth-science%252Ffamily-court-backs-parents-on-removal-of-gonads-from-intersex-child%252Fnews-story%252F60df936c557e2e21707eb198f1300276%26memtype%3Danonymous%26mode%3Dpremium&upid=rjdl4pv&upv=1.1.0 December 4, 2021 March 19, 2017 The AustralianOverington Caroline Caroline Overington December 8, 2016 Carla's case ignites firestorm among intersex community on need for surgery http://www.theaustralian.com.au/national-affairs/health/carlas-case-ignites-firestorm-among-intersex-community-on-need-for-surgery/news-story/7b1d478b8c606eaa611471f70c458df0 live https://web.archive.org/web/20211204014803/https://insight.adsrvr.org/track/up?adv=vrges6n&ref=https%3A%2F%2Fwww.theaustralian.com.au%2Fsubscribe%2Fnews%2F1%2F%3FsourceCode%3DTAWEB_WRE170_a%26dest%3Dhttps%253A%252F%252Fwww.theaustralian.com.au%252Fnational-affairs%252Fhealth%252Fcarlas-case-ignites-firestorm-among-intersex-community-on-need-for-surgery%252Fnews-story%252F7b1d478b8c606eaa611471f70c458df0%26memtype%3Danonymous%26mode%3Dpremium&upid=rjdl4pv&upv=1.1.0 December 4, 2021 March 19, 2017 The AustralianCopland Simon December 15, 2016 The medical community's approach to intersex people is still primarily focused on 'normalising' surgeries http://www.sbs.com.au/topics/sexuality/agenda/article/2016/12/15/medical-communitys-approach-intersex-people-still-primarily-focused-normalising dead https://web.archive.org/web/20170131201328/http://www.sbs.com.au/topics/sexuality/agenda/article/2016/12/15/medical-communitys-approach-intersex-people-still-primarily-focused-normalising 2017-01-31 2017-02-05 SBS and international media.Dunlop Greg December 7, 2016 Australian court approves intersex child's surgery https://www.bbc.com/news/world-australia-38218115 live https://web.archive.org/web/20190505130338/https://www.bbc.com/news/world-australia-38218115 May 5, 2019 June 22, 2018 BBC News The judge ruled that parents were able to authorize the sterilization of their 5-year-old child reported only as "Carla". The child had previously been subjected to intersex medical interventions including a clitorectomy and labiaplasty, without requiring Court oversight, which were described by the judge as surgeries that "enhanced the appearance of her female genitalia". Organisation Intersex International Australia found this "disturbing", and stated that the case was reliant on gender stereotyping and failed to take account of data on cancer risks.Carpenter Morgan Morgan Carpenter December 8, 2016 The Family Court case Re: Carla (Medical procedure) [2016] FamCA 7 https://oii.org.au/31036/re-carla-family-court/ dead https://web.archive.org/web/20170203164110/https://oii.org.au/31036/re-carla-family-court/ 2017-02-03 2017-02-02 Organisation Intersex International Australia See also Inborn errors of steroid metabolism Disorders of sexual development Intersex 17β-Hydroxysteroid dehydrogenase 17β-Hydroxysteroid dehydrogenase Type III Sex hormone (androgen/estrogen) References Further reading Bissonnette Bruno https://books.google.com/books?id=uRR1MYa-w5wC&q=17-beta-hydroxysteroid+dehydrogenase+III+deficiency Syndromes: Rapid Recognition and Perioperative Implications 2006 McGraw Hill Professional 9780071354554 en 11 March 2017 disease External links LD2A.3 E29.1 257.2 264300 C537805 32638 50658006 5659 46,XY disorder of sex development due to 17-beta-hydroxysteroid dehydrogenase 3 deficiency 752 Q4552290 collapsed Category:Autosomal recessive disorders Category:Cholesterol and steroid metabolism disorders Category:Endocrine gonad disorders Category:Intersex variations