5-alpha-reductase deficiency
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2008-06-16T16:37:21Z
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/* Signs */
{{Infobox_Disease |
Name = 5-alpha-reductase deficiency |
Image = Androstanolone.svg |
Caption = [[5-alpha reductase]] produces [[dihydrotestosterone]] |
DiseasesDB = 11 |
ICD10 = {{ICD10|E|29|1|e|20}}, {{ICD10|Q|56|3|q|50}} |
ICD9 = {{ICD9|257.2}}, {{ICD9|752.7}} |
ICDO = |
OMIM = 264600 |
MedlinePlus = |
eMedicineSubj = ped |
eMedicineTopic = 1980 |
MeshName = |
MeshNumber = |
}}
'''5-alpha-reductase deficiency''' ('''5-ARD''') is an [[autosomal recessive]] [[Intersexuality|intersex]] condition caused by a [[genetic mutation|mutation]] of the [[5-alpha reductase]] type 2 [[gene]].<ref name="Gpnotebook">{{GPnotebook|852492298|5-alpha reductase deficiency}}</ref>
==Normal function==
[[5-alpha-reductase]] is an [[enzyme]] that converts [[testosterone]] to [[dihydrotestosterone]] (DHT) in peripheral tissues. 5-alpha-reductase deficiency-2 is biochemically characterized by low to low normal levels of testosterone and decreased levels of 5α-DHT, creating a higher testosterone/DHT ratio.
[[Image:Test biosynth 5ARD2.jpg|thumb|center|600px| Biochemical effects of 5-alpha-reductase deficiency-2 in testosterone biosynthesis. Typically levels of testosterone are elevated, while levels of DHT are significantly decreased, leading to male [[undervirilization]].]]
DHT is a potent [[androgen]], necessary for the development of male external [[genitalia]] in utero.
==Signs==
The condition affects only males (i.e. those with a [[Y chromosome]]) because DHT has no known role in female development.<ref>[http://www.emedicine.com/ped/topic1980.htm eMedicine article on 5-ARD]</ref>
Individuals with 5-ARD can have normal male external genitalia, [[ambiguous genitalia]], or normal female genitalia. They are born with [[male]] [[gonad]]s, including [[testicles]] and [[Wolffian structures]], but usually appear to have [[female]] [[primary sex characteristic]]s. Consequently they are often raised as girls and may develop a female [[gender identity]]. Individuals with obvious [[virilisation|undervirilisation]] at birth, e.g. [[hypospadias]], [[micropenis]], or complete [[ambiguous genitalia]], are currently raised as boys.
Individuals with 5-ARD are generally capable of producing viable [[sperm]]. In individuals with feminised or ambiguous genitalia, there is a tendency towards a [[clitoromegaly|macroclitoris]] or microphallus, and the [[urethra]] may attach to the phallus. This structure may be capable of ejaculations as well as erections, however [[artificial insemination]] techniques or [[in-vitro fertilisation]] are necessary, due to one's inability to engage in [[sexual intercourse|intercourse]].
At [[puberty]], individuals often have primary [[amenorrhoea]], and may experience [[virilisation]]. This may include descending of the testes, [[hirsutism]] (facial/body hair considered normal in males --not to be confused with [[hypertrichosis]]), and deepening of the voice. In adulthood, individuals do not experience male-pattern baldness.<ref name="Gpnotebook"/> As DHT is a far more potent androgen than testosterone alone, virilisation in those lacking DHT may be absent or reduced compared to males with functional 5-alpha reductase. It is hypothesized that rising testosterone levels at the start of puberty (around age twelve) are able to generate sufficient levels of DHT by either the action of 5-alpha-reductase type 1 (active in the adult liver, non-genital skin and some brain areas) or through the expression of low levels of 5-alpha-reductase type 2 in the testes.
==Complications==
With 5-ARD there is a risk of gender identity disorder as well as infertility, due to underdevelopment of seminal vesicles and prostate.
===Gender identity disorder===
Although most people with 5-ARD identify themselves as females, some may develop a male gender identity coinciding with the pubertal [[virilisation]], or can present themselves with apparent gender dysphoria and transgender behavior. Most cases of gender (role) changes have been reported in large families in the Dominican Republic and [[São Paulo]]. It is unclear if these patients had the means or possibilities to be treated against virilisation. In some cultures it seems to be socially more beneficial to be a man than an infertile woman. It is unclear whether this has played any part in the above mentioned gender changes.
===Infertility===
There is an increased risk of [[cryptorchidism]] in 5-ARD, causing infertility, but also a higher risk of [[testicular cancer]]. Fertility is further compromised by the underdevelopment of seminal vesicles and prostate.
On the other hand, fertility depending on the female characteristics are impossible; Although the external genitalia appear female, the "pseudovagina" consists only of the lower two-thirds of a normal vagina, creating a blind-ending vaginal pouch. Due to the normal action of [[Anti-müllerian hormone|Müllerian inhibiting factor]] produced by the [[testis]] in utero, individuals with 5-ARD lack a [[uterus]] and [[Fallopian tube]]s. Thus, individuals with 5-ARD are not able to carry a pregnancy, and since they have testes, and not ovaries, they are unable to create ova preventing infertility treatments such as surrogate motherhood.
==Prevalence==
The number of people with this condition varies geographically, depending on how much of a given population is interrelated. In 1974, Jullianne Imperato-McGinley has estimated an incidence of 1:90 males in the Dominican Republic. This can be seen in that certain regions have evolved terminology for the condition:
===Local names===
The term '''Guevedoche''' or Guevedoces is Spanish slang for the condition. It originated in the [[Dominican Republic]] where more than three dozen cases have occurred in the small village of Salinas, all descended from a single individual named Altagracia Carrasco. It stands for the vulgar expression ''huevo a los doce'', which translates literally as "eggs at twelve" ("eggs" being a common slang term for "testicles"). It is also known locally as 'Machihembras' (Literally 'Malefemale').
A similar cluster of cases among the Simbari of the Eastern Highlands of [[Papua New Guinea]] has the local name 'Kwolu-aatmwol' ('female thing transforming into male thing').
== Popular culture ==
* [[Jeffrey Eugenides]] won a [[Pulitzer Prize]] for his [[2002]] novel ''[[Middlesex (novel)|Middlesex]]'', which explores this deficiency.
* [[Dr. Quentin Costa]], a character on the television show ''[[Nip/Tuck]]'', has this condition.
* Documentaries on the condition include "Guevote: The Way I Feel Is How I Am" ("Guevote: So wie ich mich fuehle, bin ich"), 1996, by filmmaker Rolando Sánchez,<ref>[http://www.german-cinema.de/app/filmarchive/film_view.php?film_id=131 Guevote - The Way I Feel Is How I Am (Guevote - So wie ich mich fühle, bin ich)]</ref> and "The Fight to be Male", 1979, British Broadcasting Company.
==References==
{{reflist}}
==See also==
*[[Third sex]]
*[[Intersexuality]]
:*[[17-beta-hydroxysteroid dehydrogenase deficiency]]
:*[[Androgen insensitivity syndrome]]
:*[[Gonadal dysgenesis]]
==External links==
*[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=264600 OMIM article]
*[http://www.emedicine.com/ped/topic1980.htm 5-Alpha-Reductase Deficiency at eMedicine]
*[http://www.newint.org/issue300/trans.html "Whatever I feel..."] Article in the New Internationalist
{{Endocrine pathology}}
[[Category:Intersexuality]]
[[Category:Endocrinology]]