Disorder of sexual development by 5 α -reductase 2 deficiency

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5 α- reductase-2 deficiency is an autosomal recessive hereditary disease in humans, which can lead to a disorder of sexual development . It is based on a deficiency of the enzyme steroid 5- α -reductase type 2 Affected genetically male (XY) patients have a rare male, sexually ambiguous up to complete female phenotype on. Genetically female (XX) affected persons do not develop any symptoms ( gender-limited phenotype expression ).

Synonyms are: 5-alpha reductase deficiency; 46, XY DSD due to 5-alpha reductase-2 deficiency; Pseudohermaphroditism, male, due to 5-alpha-reductase-2 deficiency; Pseudovaginal perineoscrotal hypospadias; Steroid 5 Alpha Reductase 2 Deficiency

A regional occurrence of 5α-reductase-2 deficiency is particularly noticeable in the Dominican Republic as well as in Turkey , Mexico , Egypt and New Guinea .

Clinical picture

Dihydrotestosterone

The 5 α -reductase (SRD5) converts the sex hormone testosterone into its most biologically active form dihydrotestosterone (DHT) in the target cells . This form is one of the androgens and their effects on the relevant androgen receptor is much stronger than that of testosterone. DHT is responsible, among other things, for the formation of the internal and external male genitals during embryonic development in the womb .

If no due to a lack of steroid 5 α -reductase (in particular of the second isozyme SRD5A2 ) the conversion of testosterone to DHT, it may during pregnancy in male fetus to form a pseudohermaphroditism with a hypospadias of the penis to come, in which the outer opening the urethra is in the perineal area. In female unborn babies, the enzyme deficiency does not affect the development of the body.

Biochemically, the testosterone concentration in those affected is low to normal. The DHT level is very low. The ratio of testosterone to DHT is thus higher than normal.

Symptoms

Affected boys are born with testicles , but in the first few years these are hidden inside the body ( cryptorchidism ). There are predominantly female external genitalia with an enlarged clitoris or just a small penis, which is associated with hypospadias of varying degrees. Affected children are mostly raised like girls and initially develop a more feminine gender identity in early childhood. It is not uncommon for those affected to develop clear signs of male gender identity even before the onset of puberty .

At the onset of puberty there is then an increased release of the sex hormone testosterone. The supposed girls go through male puberty. The testicles that have so far remained inside the body descend and step out into a scrotum that is forming. The previously mostly ambiguous clitoris enlarges or grows into a penis.

genetics

Underlying mutations of the 5α-reductase-2 gene ( SRD5A2 gene ) are diverse, but often affect exon 2 and exon 4 . In addition to homozygous mutations, different mutations also occur in both alleles (compound heterozygosity).

Social

In the remote village of Las Salinas in the Dominican Republic, an occurrence in 12 of 13 families was recorded in 1974. One in 90 men was affected. All of these cases can be traced back to a common direct ancestor, which is why a founder effect was discussed. The term Guevedoche or Guevedoces also comes from the village of Salinas , which means something like "eggs with 12" in Spanish ( guevas is a slang term for testicles, doce means twelve). Sometimes the explanation "penis at twelve" is used in both English and German. The term machihembras (literally “male-female”) is also used.

More than 85% of those affected lived with male gender identity after puberty, which was taken as evidence of the paramount role of testosterone in the development of male gender identity. After the first author of the cited studies a pronounced disorder of sex development due to 5 is α -reductase deficiency as Imperato-McGinley syndrome called.

literature

  • Elaine MF Costa, Sorahia Domenice, Maria Helena Sircili, Marlene Inacio, Berenice B. Mendonca: DSD Due to 5α-Reductase 2 Deficiency - from Diagnosis to Long Term Outcome. In: Seminars in Reproductive Medicine. October 2012, Volume 30, No. 5, pp. 427-431, doi: 10.1055 / s-0032-1324727 ( full text ).

Individual evidence

  1. ↑ Elaine MF Costa, Sorahia Domenice, Maria Helena Sircili, Marlene Inacio, Berenice B. Mendonca: DSD Due to 5α-Reductase 2 Deficiency - from Diagnosis to Long Term Outcome. In: Seminars in Reproductive Medicine. October 2012, Volume 30, No. 5, pp. 427-431, doi: 10.1055 / s-0032-1324727 .
  2. ↑ Hey-Joo Kang, Julianne Imperato-McGinley, Yuan-Shan Zhu, Zev Rosenwaks: The effect of 5α-reductase-2 deficiency on human fertility. In: Fertility and sterility. Volume 101, No. 2, January 2014, pp. 310-316, doi: 10.1016 / j.fertnstert.2013.11.128 ; Chapter: Gender Identity and Gender Role.
  3. ↑ PSEUDOVAGINAL PERINEOSCROTAL HYPOSPADIAS. (No longer available online.) Online Mendelian Inheritance in Man, archived from the original on March 5, 2010 ; Retrieved April 16, 2010 . Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. @1@ 2Template: Webachiv / IABot / www.ncbi.nlm.nih.gov
  4. ↑ a b L. Maimoun, P. Philibert, B. Cammas et al .: Phenotypical, biological, and molecular heterogeneity of 5alpha-reductase deficiency: an extensive international experience of 55 patients. In: The Journal of clinical endocrinology and metabolism . Volume 96, Number 2, February 2011, pp. 296-307, ISSN  1945-7197 , doi: 10.1210 / jc.2010-1024 , PMID 21147889 .
  5. ↑ Rachael Rettner: 'Guevedoces': Rare Medical Condition Hides Child's Sex Until Age 12 . On: livescience.com September 21, 2015; last accessed on June 22, 2016.
  6. ↑ Julianne Imperato-McGinley, Yuan-Shan Zhu: Androgens and male physiology — The syndrome of 5 alpha-reductase-2 deficiency. In: Molecular and Cellular Endocrinology. Volume 19, No. 1, December 2002, pp. 51-59, doi: 10.1016 / S0303-7207 (02) 00368-4 ( full text ).
  7. ↑ Hey-Joo Kang, Julianne Imperato-McGinley, Yuan-Shan Zhu, Zev Rosenwaks: The effect of 5α-reductase-2 deficiency on human fertility. In: Fertility and sterility. Volume 101, No. 2, January 2014, pp. 310-316, doi: 10.1016 / j.fertnstert.2013.11.128 ( full text ).
  8. ↑ Picture: Mutations in the SRD5A2 gene on: marlin-prod.literatumonline.com ; accessed on February 23, 2019.
  9. Jump up ↑ J. Imperato-McGinley, L. Guerrero, T. Gautier, RE Peterson: Steroid 5alpha-reductase deficiency in man: an inherited form of male pseudohermaphroditism. In: Science. Volume 186, Number 4170, December 1974, pp. 1213-1215, ISSN  0036-8075 , PMID 4432067 .
  10. ↑ The 'Guevedoces' of the Dominican Republic. Urological Sciences Research Foundation. Retrieved February 22, 2013.
  11. ^ J. Imperato-McGinley, RE Peterson, T. Gautier, E. Sturla: Androgens and the evolution of male-gender identity among male pseudohermaphrodites with 5alpha-reductase deficiency. In: The New England Journal of Medicine . Volume 300, Number 22, May 1979, pp. 1233-1237, ISSN  0028-4793 , doi: 10.1056 / NEJM197905313002201 , PMID 431680 .
  12. ^ P. Hertoft, T. Sørensen: Transsexuality: Some remarks based on clinical experience . In: R. Porter, J. Whelan (Eds.): Sex, Hormones and Behavior . Ciba Foundation Symposium 62nd Exzerpt Medica, Amsterdam, Oxford, New York 1979, ISBN 90-219-4068-X , p. 192 (English, [1] ).

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