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5-alpha reductase deficiency

Reviewed April 2008

What is 5-alpha reductase deficiency?

5-alpha reductase deficiency is a condition that affects male sexual development before birth and during puberty. People with this condition are genetically male, with one X and one Y chromosome in each cell, and they have male gonads (testes). Their bodies, however, do not produce enough of a hormone called dihydrotestosterone (DHT). DHT has a critical role in male sexual development, and a shortage of this hormone disrupts the formation of the external sex organs before birth.

Many people with 5-alpha reductase deficiency are born with external genitalia that appear female. In other cases, the external genitalia do not look clearly male or clearly female (sometimes called ambiguous genitalia). Still other affected infants have genitalia that appear predominantly male, often with an unusually small penis (micropenis) and the urethra opening on the underside of the penis (hypospadias).

During puberty, people with this condition develop some secondary sex characteristics, such as increased muscle mass, deepening of the voice, development of pubic hair, and a growth spurt. The penis and scrotum (the sac of skin that holds the testes) grow larger. Unlike many men, people with 5-alpha reductase deficiency do not develop much facial or body hair. Most affected males are unable to father a child (infertile).

Children with 5-alpha reductase deficiency are often raised as girls. About half of these individuals adopt a male gender role in adolescence or early adulthood.

How common is 5-alpha reductase deficiency?

5-alpha reductase deficiency is a rare condition; the exact incidence is unknown. Large families with affected members have been found in several countries, including the Dominican Republic, Papua New Guinea, Turkey, and Egypt.

What genes are related to 5-alpha reductase deficiency?

Mutations in the SRD5A2 gene cause 5-alpha reductase deficiency. The SRD5A2 gene provides instructions for making an enzyme called steroid 5-alpha reductase 2. This enzyme is involved in processing androgens, which are hormones that direct male sexual development. Specifically, the enzyme is responsible for a chemical reaction that converts the hormone testosterone to DHT. DHT is essential for the normal development of male sex characteristics before birth, particularly the formation of the external genitalia.

Mutations in the SRD5A2 gene prevent steroid 5-alpha reductase 2 from effectively converting testosterone to DHT in the developing reproductive tissues. These hormonal factors underlie the changes in male sexual development seen in infants with 5-alpha reductase deficiency.

During puberty, the testes produce more testosterone. Researchers believe that people with 5-alpha reductase deficiency develop secondary male sex characteristics in response to higher levels of this hormone. Some affected people also retain a small amount of 5-alpha reductase 2 activity, which may produce DHT and contribute to the development of secondary sex characteristics during puberty.

Related Gene(s)

Changes in this gene are associated with 5-alpha reductase deficiency.

  • SRD5A2

How do people inherit 5-alpha reductase deficiency?

This condition is inherited in an autosomal recessive pattern, which means both copies of the SRD5A2 gene in each cell have mutations. Most often, the parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but do not show signs and symptoms of the condition.

Although people who are genetically female (with two X chromosomes in each cell) may inherit mutations in both copies of the SRD5A2 gene, their sexual development is not affected. The development of female sex characteristics does not require DHT, so a lack of steroid 5-alpha reductase 2 activity does not cause physical changes in these individuals. Only people who have mutations in both copies of the SRD5A2 gene and are genetically male (with one X and one Y chromosome in each cell) have the characteristic signs of 5-alpha reductase deficiency.

Where can I find information about diagnosis or management of 5-alpha reductase deficiency?

These resources address the diagnosis or management of 5-alpha reductase deficiency and may include treatment providers.

  • Genetic Testing Registry: 3-Oxo-5 alpha-steroid delta 4-dehydrogenase deficiency (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0268297)
  • MedlinePlus Encyclopedia: Ambiguous Genitalia (http://www.nlm.nih.gov/medlineplus/ency/article/003269.htm)
  • MedlinePlus Encyclopedia: Intersex (http://www.nlm.nih.gov/medlineplus/ency/article/001669.htm)

You might also find information on the diagnosis or management of 5-alpha reductase deficiency in Educational resources (http://www.ghr.nlm.nih.gov/condition/5-alpha-reductase-deficiency/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/5-alpha-reductase-deficiency/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about 5-alpha reductase deficiency?

You may find the following resources about 5-alpha reductase deficiency helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for 5-alpha reductase deficiency?

  • Familial incomplete male pseudohermaphroditism, type 2
  • male pseudohermaphroditism due to 5-alpha-reductase deficiency
  • PPSH
  • Pseudovaginal perineoscrotal hypospadias
  • Steroid 5-alpha-reductase deficiency

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about 5-alpha reductase deficiency?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding 5-alpha reductase deficiency?

androgens ; autosomal ; autosomal recessive ; cell ; chromosome ; deficiency ; DHT ; dihydrotestosterone ; enzyme ; familial ; gene ; genitalia ; hormone ; hypospadias ; incidence ; infertile ; micropenis ; puberty ; recessive ; scrotum ; testes ; testosterone

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Bahceci M, Ersay AR, Tuzcu A, Hiort O, Richter-Unruh A, Gokalp D. A novel missense mutation of 5-alpha reductase type 2 gene (SRD5A2) leads to severe male pseudohermaphroditism in a Turkish family. Urology. 2005 Aug;66(2):407-10. (http://www.ncbi.nlm.nih.gov/pubmed/16098368?dopt=Abstract)
  • Baldinotti F, Majore S, Fogli A, Marrocco G, Ghirri P, Vuerich M, Tumini S, Boscherini B, Vetri M, Scommegna S, Rinaldi R, Simi P, Grammatico P. Molecular characterization of 6 unrelated Italian patients with 5alpha-reductase type 2 deficiency. J Androl. 2008 Jan-Feb;29(1):20-8. Epub 2007 Jul 3. (http://www.ncbi.nlm.nih.gov/pubmed/17609295?dopt=Abstract)
  • Cai LQ, Zhu YS, Katz MD, Herrera C, Baéz J, DeFillo-Ricart M, Shackleton CH, Imperato-McGinley J. 5 alpha-reductase-2 gene mutations in the Dominican Republic. J Clin Endocrinol Metab. 1996 May;81(5):1730-5. (http://www.ncbi.nlm.nih.gov/pubmed/8626825?dopt=Abstract)
  • Cohen-Kettenis PT. Gender change in 46,XY persons with 5alpha-reductase-2 deficiency and 17beta-hydroxysteroid dehydrogenase-3 deficiency. Arch Sex Behav. 2005 Aug;34(4):399-410. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16010463?dopt=Abstract)
  • Hackel C, Oliveira LE, Ferraz LF, Tonini MM, Silva DN, Toralles MB, Stuchi-Perez EG, Guerra-Junior G. New mutations, hotspots, and founder effects in Brazilian patients with steroid 5alpha-reductase deficiency type 2. J Mol Med (Berl). 2005 Jul;83(7):569-76. Epub 2005 Mar 16. (http://www.ncbi.nlm.nih.gov/pubmed/15770495?dopt=Abstract)
  • Hochberg Z, Chayen R, Reiss N, Falik Z, Makler A, Munichor M, Farkas A, Goldfarb H, Ohana N, Hiort O. Clinical, biochemical, and genetic findings in a large pedigree of male and female patients with 5 alpha-reductase 2 deficiency. J Clin Endocrinol Metab. 1996 Aug;81(8):2821-7. (http://www.ncbi.nlm.nih.gov/pubmed/8768837?dopt=Abstract)
  • Sinnecker GH, Hiort O, Dibbelt L, Albers N, Dörr HG, Hauss H, Heinrich U, Hemminghaus M, Hoepffner W, Holder M, Schnabel D, Kruse K. Phenotypic classification of male pseudohermaphroditism due to steroid 5 alpha-reductase 2 deficiency. Am J Med Genet. 1996 May 3;63(1):223-30. (http://www.ncbi.nlm.nih.gov/pubmed/8723114?dopt=Abstract)
  • Sultan C, Lumbroso S, Paris F, Jeandel C, Terouanne B, Belon C, Audran F, Poujol N, Georget V, Gobinet J, Jalaguier S, Auzou G, Nicolas JC. Disorders of androgen action. Semin Reprod Med. 2002 Aug;20(3):217-28. Review. (http://www.ncbi.nlm.nih.gov/pubmed/12428202?dopt=Abstract)
  • Wilson JD, Griffin JE, Russell DW. Steroid 5 alpha-reductase 2 deficiency. Endocr Rev. 1993 Oct;14(5):577-93. Review. (http://www.ncbi.nlm.nih.gov/pubmed/8262007?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: April 2008
Published: April 21, 2014