Reviewed April 2015
What is 3-beta-hydroxysteroid dehydrogenase deficiency?
3-beta (β)-hydroxysteroid dehydrogenase (HSD) deficiency is an inherited disorder that affects hormone-producing glands including the gonads (ovaries in females and testes in males) and the adrenal glands. The gonads direct sexual development before birth and during puberty. The adrenal glands, which are located on top of the kidneys, regulate the production of certain hormones and control salt levels in the body. People with 3β-HSD deficiency lack many of the hormones that are made in these glands. 3β-HSD deficiency is one of a group of disorders known as congenital adrenal hyperplasias that impair hormone production and disrupt sexual development and maturation.
There are three types of 3β-HSD deficiency: the salt-wasting, non-salt-wasting, and non-classic types. In the salt-wasting type, hormone production is extremely low. Individuals with this type lose large amounts of sodium in their urine, which can be life-threatening. Individuals affected with the salt-wasting type are usually diagnosed soon after birth due to complications related to a lack of salt reabsorption, including dehydration, poor feeding, and vomiting. People with the non-salt-wasting type of 3β-HSD deficiency produce enough hormone to allow sodium reabsorption in the kidneys. Individuals with the non-classic type have the mildest symptoms and do not experience salt wasting.
In males with any type of 3β-HSD deficiency, problems with male sex hormones lead to abnormalities of the external genitalia. These abnormalities range from having the opening of the urethra on the underside of the penis (hypospadias) to having external genitalia that do not look clearly male or female (ambiguous genitalia). The severity of the genital abnormality does not consistently depend on the type of the condition. Because of the hormone dysfunction in the testes, males with 3β-HSD deficiency are frequently unable to have biological children (infertile).
Females with 3β-HSD deficiency may have slight abnormalities of the external genitalia at birth. Females affected with the non-salt-wasting or non-classic types are typically not diagnosed until mid-childhood or puberty, when they may experience irregular menstruation, premature pubic hair growth, and excessive body hair growth (hirsutism). Females with 3β-HSD deficiency have difficulty conceiving a child (impaired fertility).
How common is 3-beta-hydroxysteroid dehydrogenase deficiency?
The exact prevalence of 3β-HSD deficiency is unknown. At least 60 affected individuals have been reported.
What genes are related to 3-beta-hydroxysteroid dehydrogenase deficiency?
Mutations in the HSD3B2 gene cause 3β-HSD deficiency. The HSD3B2 gene provides instructions for making the 3β-HSD enzyme. This enzyme is found in the gonads and adrenal glands. The 3β-HSD enzyme is involved in the production of many hormones, including cortisol, aldosterone, androgens, and estrogen. Cortisol has numerous functions such as maintaining energy and blood sugar levels, protecting the body from stress, and suppressing inflammation. Aldosterone is sometimes called the salt-retaining hormone because it regulates the amount of salt retained by the kidney. The retention of salt affects fluid levels and blood pressure. Androgens and estrogen are essential for normal sexual development and reproduction.
3β-HSD deficiency is caused by a deficiency (shortage) of the 3β-HSD enzyme. The amount of functional 3β-HSD enzyme determines whether a person will have the salt-wasting or non-salt-wasting type of the disorder. Individuals with the salt-wasting type have HSD3B2 gene mutations that result in the production of very little or no enzyme. People with the non-salt-wasting type of this condition have HSD3B2 gene mutations that allow the production of some functional enzyme, although in reduced amounts.
Changes in this gene are associated with 3-beta-hydroxysteroid dehydrogenase deficiency.
How do people inherit 3-beta-hydroxysteroid dehydrogenase 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.
Where can I find information about diagnosis or management of 3-beta-hydroxysteroid dehydrogenase deficiency?
These resources address the diagnosis or management of 3-beta-hydroxysteroid dehydrogenase deficiency and may include treatment providers.
- Genetic Testing Registry: 3 beta-Hydroxysteroid dehydrogenase deficiency (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0342471)
- Great Ormond Street Hospital for Children: Cortisol Deficiency (http://www.gosh.nhs.uk/medical-information/search-medical-conditions/cortisol-deficiency)
- MedlinePlus Encyclopedia: Ambiguous Genitalia (http://www.nlm.nih.gov/medlineplus/ency/article/003269.htm)
- MedlinePlus Encyclopedia: Congenital Adrenal Hyperplasia (http://www.nlm.nih.gov/medlineplus/ency/article/000411.htm)
- National Institutes of Health Clinical Center: Managing Adrenal Insufficiency (http://www.cc.nih.gov/ccc/patient_education/pepubs/mngadrins.pdf)
You might also find information on the diagnosis or management of 3-beta-hydroxysteroid dehydrogenase deficiency in
Educational resources and 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 3-beta-hydroxysteroid dehydrogenase deficiency?
You may find the following resources about 3-beta-hydroxysteroid dehydrogenase deficiency helpful. These materials are written for the general public.
MedlinePlus - Health information
- Encyclopedia: Ambiguous Genitalia (http://www.nlm.nih.gov/medlineplus/ency/article/003269.htm)
- Encyclopedia: Congenital Adrenal Hyperplasia (http://www.nlm.nih.gov/medlineplus/ency/article/000411.htm)
- Health Topic: Adrenal Gland Disorders (http://www.nlm.nih.gov/medlineplus/adrenalglanddisorders.html)
- Health Topic: Infertility (http://www.nlm.nih.gov/medlineplus/infertility.html)
Educational resources - Information pages
- Boston Children's Hospital: Congenital Adrenal Hyperplasia (http://www.childrenshospital.org/conditions-and-treatments/conditions/c/congenital-adrenal-hyperplasia-cah)
- CARES Foundation: FAQs (http://www.caresfoundation.org/faqs/)
- Disease InfoSearch: 3-Beta-Hydroxysteroid Dehydrogenase Deficiency (http://www.diseaseinfosearch.org/3-Beta-Hydroxysteroid+Dehydrogenase+Deficiency/30)
- March of Dimes: Genital and Urinary Tract Defects (http://www.marchofdimes.org/baby/genital-and-urinary-tract-defects.aspx)
- Orphanet: Congenital adrenal hyperplasia due to 3-beta-hydroxysteroid dehydrogenase deficiency (http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=90791)
Patient support - For patients and families
- CARES Foundation (http://www.caresfoundation.org/)
- National Organization for Rare Disorders (NORD): Congenital Adrenal Hyperplasia (https://rarediseases.org/rare-diseases/congenital-adrenal-hyperplasia/)
- RESOLVE: The National Infertility Association (http://www.resolve.org/)
- The MAGIC Foundation: Congenital Adrenal Hyperplasia (http://www.magicfoundation.org/www/docs/100/congenital_adrenal_hyperplasia.html)
- University of Kansas Medical Center Resource List: Sexuality and Sexual Differentiation Syndromes (http://www.kumc.edu/gec/support/ambig.html)
You may also be interested in these resources, which are designed for healthcare professionals and researchers.
Genetic Testing Registry - Repository of genetic test information
- Genetic Testing Registry: 3 beta-Hydroxysteroid dehydrogenase deficiency (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0342471)
- ClinicalTrials.gov - Linking patients to medical research (https://clinicaltrials.gov/ct2/results?cond=%223-beta-hydroxysteroid%20dehydrogenase%20deficiency%22%20OR%20%22Adrenal%20Hyperplasia%2C%20Congenital%22)
- PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/pubmed?term=%28%283%20beta%20hydroxysteroid%20dehydrogenase%20deficiency%5BTIAB%5D%29%20OR%20%283%20beta%20HSD%20deficiency%5BTIAB%5D%29%20OR%20%283beta%20hydroxysteroid%20dehydrogenase%20deficiency%5BTIAB%5D%29%20OR%20%283beta%20HSD%20deficiency%29%29%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%203600%20days%22%5Bdp%5D)
- OMIM - Genetic disorder catalog (http://omim.org/entry/201810)
What other names do people use for 3-beta-hydroxysteroid dehydrogenase deficiency?
- 3 beta-HSD deficiency
- 3β-HSD deficiency
- 3β-HSD deficiency congenital adrenal hyperplasia
- 3β-hydroxysteroid dehydrogenase deficiency
- 3 beta-ol dehydrogenase deficiency
- 3b-hydroxysteroid dehydrogenase deficiency
- type II 3β-hydroxysteroid dehydrogenase deficiency
For more information about naming genetic conditions, see the Genetics Home Reference
Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide)
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 3-beta-hydroxysteroid dehydrogenase deficiency?
Ask the Genetic and Rare Diseases Information Center (https://rarediseases.info.nih.gov/gard).
What glossary definitions help with understanding 3-beta-hydroxysteroid dehydrogenase deficiency?
adrenal glands ;
autosomal recessive ;
difficulty conceiving ;
You may find definitions for these and many other terms in the Genetics Home Reference
- Lutfallah C, Wang W, Mason JI, Chang YT, Haider A, Rich B, Castro-Magana M, Copeland KC, David R, Pang S. Newly proposed hormonal criteria via genotypic proof for type II 3beta-hydroxysteroid dehydrogenase deficiency. J Clin Endocrinol Metab. 2002 Jun;87(6):2611-22. (http://www.ncbi.nlm.nih.gov/pubmed/12050224?dopt=Abstract)
- Pang S, Carbunaru G, Haider A, Copeland KC, Chang YT, Lutfallah C, Mason JI. Carriers for type II 3beta-hydroxysteroid dehydrogenase (HSD3B2) deficiency can only be identified by HSD3B2 genotype study and not by hormone test. Clin Endocrinol (Oxf). 2003 Mar;58(3):323-31. (http://www.ncbi.nlm.nih.gov/pubmed/12608938?dopt=Abstract)
- Pang S, Wang W, Rich B, David R, Chang YT, Carbunaru G, Myers SE, Howie AF, Smillie KJ, Mason JI. A novel nonstop mutation in the stop codon and a novel missense mutation in the type II 3beta-hydroxysteroid dehydrogenase (3beta-HSD) gene causing, respectively, nonclassic and classic 3beta-HSD deficiency congenital adrenal hyperplasia. J Clin Endocrinol Metab. 2002 Jun;87(6):2556-63. (http://www.ncbi.nlm.nih.gov/pubmed/12050213?dopt=Abstract)
- Pang S. Congenital adrenal hyperplasia owing to 3 beta-hydroxysteroid dehydrogenase deficiency. Endocrinol Metab Clin North Am. 2001 Mar;30(1):81-99, vi-vii. Review. (http://www.ncbi.nlm.nih.gov/pubmed/11344940?dopt=Abstract)
- Pan Y, Zhong S, Hu RM, Gong W. Mutation of 3β-hydroxysteroid dehydrogenase (3β-HSD) at the 3'-untranslated region is associated with adrenocortical insufficiency. Mol Med Rep. 2012 Dec;6(6):1305-8. doi: 10.3892/mmr.2012.1107. Epub 2012 Sep 28. (http://www.ncbi.nlm.nih.gov/pubmed/23026940?dopt=Abstract)
- Simard J, Moisan AM, Morel Y. Congenital adrenal hyperplasia due to 3beta-hydroxysteroid dehydrogenase/Delta(5)-Delta(4) isomerase deficiency. Semin Reprod Med. 2002 Aug;20(3):255-76. Review. (http://www.ncbi.nlm.nih.gov/pubmed/12428206?dopt=Abstract)
- Takasawa K, Ono M, Hijikata A, Matsubara Y, Katsumata N, Takagi M, Morio T, Ohara O, Kashimada K, Mizutani S. Two novel HSD3B2 missense mutations with diverse residual enzymatic activities for Δ5-steroids. Clin Endocrinol (Oxf). 2014 Jun;80(6):782-9. doi: 10.1111/cen.12394. Epub 2014 Jan 16. (http://www.ncbi.nlm.nih.gov/pubmed/24372086?dopt=Abstract)
- Welzel M, Wüstemann N, Simic-Schleicher G, Dörr HG, Schulze E, Shaikh G, Clayton P, Grötzinger J, Holterhus PM, Riepe FG. Carboxyl-terminal mutations in 3beta-hydroxysteroid dehydrogenase type II cause severe salt-wasting congenital adrenal hyperplasia. J Clin Endocrinol Metab. 2008 Apr;93(4):1418-25. doi: 10.1210/jc.2007-1874. Epub 2008 Feb 5. (http://www.ncbi.nlm.nih.gov/pubmed/18252794?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
See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.