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Genetics Home Reference: your guide to understanding genetic conditions
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17-beta hydroxysteroid dehydrogenase 3 deficiency

Reviewed November 2008

What is 17-beta hydroxysteroid dehydrogenase 3 deficiency?

17-beta hydroxysteroid dehydrogenase 3 deficiency is a condition that affects male sexual development. 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 the male sex hormone testosterone. Testosterone has a critical role in male sexual development, and a shortage of this hormone disrupts the formation of the external sex organs before birth.

Most people with 17-beta hydroxysteroid dehydrogenase 3 deficiency are born with external genitalia that appear female. In some 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) or 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, and development of male pattern body hair. The penis and scrotum (the sac of skin that holds the testes) grow larger during this period. In addition to these changes typical of adolescent boys, some affected males may also experience breast enlargement (gynecomastia). Men with this disorder are generally unable to father children (infertile).

Children with 17-beta hydroxysteroid dehydrogenase 3 deficiency are often raised as girls. About half of these individuals adopt a male gender role in adolescence or early adulthood.

How common is 17-beta hydroxysteroid dehydrogenase 3 deficiency?

17-beta hydroxysteroid dehydrogenase 3 deficiency is a rare disorder. Researchers have estimated that this condition occurs in approximately 1 in 147,000 newborns. It is more common in the Arab population of Gaza, where it affects 1 in 200 to 300 people.

What genes are related to 17-beta hydroxysteroid dehydrogenase 3 deficiency?

Mutations in the HSD17B3 gene cause 17-beta hydroxysteroid dehydrogenase 3 deficiency. The HSD17B3 gene provides instructions for making an enzyme called 17-beta hydroxysteroid dehydrogenase 3. This enzyme is active in the testes, where it helps to produce testosterone from a precursor hormone called androstenedione.

Mutations in the HSD17B3 gene result in a 17-beta hydroxysteroid dehydrogenase 3 enzyme with little or no activity, reducing testosterone production. A shortage of testosterone affects the development of the reproductive tract in the male fetus, resulting in the abnormalities in the external sex organs that occur in 17-beta hydroxysteroid dehydrogenase 3 deficiency.

At puberty, conversion of androstenedione to testosterone increases in various tissues of the body through processes involving other enzymes. The additional testosterone results in the development of male secondary sex characteristics in adolescents, including those with 17-beta dehydrogenase 3 deficiency.

A portion of the androstenedione is also converted to the female sex hormone estrogen. Since impairment of the conversion to testosterone in this disorder results in excess androstenedione in the body, a corresponding excess of estrogen may be produced, leading to breast enlargement in some affected individuals.

Related Gene(s)

Changes in this gene are associated with 17-beta hydroxysteroid dehydrogenase 3 deficiency.

  • HSD17B3

How do people inherit 17-beta hydroxysteroid dehydrogenase 3 deficiency?

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. Individuals who are genetically male and have two copies of a mutated gene in each cell are affected by 17-beta hydroxysteroid dehydrogenase 3 deficiency. People with two mutations who are genetically female do not usually experience any signs and symptoms of this disorder.

Where can I find information about diagnosis or management of 17-beta hydroxysteroid dehydrogenase 3 deficiency?

These resources address the diagnosis or management of 17-beta hydroxysteroid dehydrogenase 3 deficiency and may include treatment providers.

  • Genetic Testing Registry: Testosterone 17-beta-dehydrogenase deficiency (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0268296)
  • 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 17-beta hydroxysteroid dehydrogenase 3 deficiency in Educational resources (http://www.ghr.nlm.nih.gov/condition/17-beta-hydroxysteroid-dehydrogenase-3-deficiency/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/17-beta-hydroxysteroid-dehydrogenase-3-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 17-beta hydroxysteroid dehydrogenase 3 deficiency?

You may find the following resources about 17-beta hydroxysteroid dehydrogenase 3 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 17-beta hydroxysteroid dehydrogenase 3 deficiency?

  • 17-beta hydroxysteroid dehydrogenase III deficiency
  • 17-ketosteroid reductase deficiency of testis
  • 17-KSR deficiency
  • neutral 17-beta-hydroxysteroid oxidoreductase deficiency
  • pseudohermaphroditism, male, with gynecomastia
  • testosterone 17-beta-dehydrogenase 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 17-beta hydroxysteroid dehydrogenase 3 deficiency?

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

What glossary definitions help with understanding 17-beta hydroxysteroid dehydrogenase 3 deficiency?

adolescent ; autosomal ; autosomal recessive ; cell ; chromosome ; deficiency ; dehydrogenase ; enzyme ; fetus ; gene ; genitalia ; gynecomastia ; hormone ; hypospadias ; infertile ; inherited ; micropenis ; oxidoreductase ; population ; precursor ; puberty ; recessive ; scrotum ; sex hormone ; testes ; testis ; 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

  • Andersson S, Geissler WM, Wu L, Davis DL, Grumbach MM, New MI, Schwarz HP, Blethen SL, Mendonca BB, Bloise W, Witchel SF, Cutler GB Jr, Griffin JE, Wilson JD, Russel DW. Molecular genetics and pathophysiology of 17 beta-hydroxysteroid dehydrogenase 3 deficiency. J Clin Endocrinol Metab. 1996 Jan;81(1):130-6. (http://www.ncbi.nlm.nih.gov/pubmed/8550739?dopt=Abstract)
  • Boehmer AL, Brinkmann AO, Sandkuijl LA, Halley DJ, Niermeijer MF, Andersson S, de Jong FH, Kayserili H, de Vroede MA, Otten BJ, Rouwé CW, Mendonça BB, Rodrigues C, Bode HH, de Ruiter PE, Delemarre-van de Waal HA, Drop SL. 17Beta-hydroxysteroid dehydrogenase-3 deficiency: diagnosis, phenotypic variability, population genetics, and worldwide distribution of ancient and de novo mutations. J Clin Endocrinol Metab. 1999 Dec;84(12):4713-21. (http://www.ncbi.nlm.nih.gov/pubmed/10599740?dopt=Abstract)
  • Faienza MF, Giordani L, Delvecchio M, Cavallo L. Clinical, endocrine, and molecular findings in 17beta-hydroxysteroid dehydrogenase type 3 deficiency. J Endocrinol Invest. 2008 Jan;31(1):85-91. Review. (http://www.ncbi.nlm.nih.gov/pubmed/18296911?dopt=Abstract)
  • Lee YS, Kirk JM, Stanhope RG, Johnston DI, Harland S, Auchus RJ, Andersson S, Hughes IA. Phenotypic variability in 17beta-hydroxysteroid dehydrogenase-3 deficiency and diagnostic pitfalls. Clin Endocrinol (Oxf). 2007 Jul;67(1):20-8. Epub 2007 Apr 27. (http://www.ncbi.nlm.nih.gov/pubmed/17466011?dopt=Abstract)
  • Moghrabi N, Hughes IA, Dunaif A, Andersson S. Deleterious missense mutations and silent polymorphism in the human 17beta-hydroxysteroid dehydrogenase 3 gene (HSD17B3). J Clin Endocrinol Metab. 1998 Aug;83(8):2855-60. (http://www.ncbi.nlm.nih.gov/pubmed/9709959?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: November 2008
Published: December 16, 2014