3 beta-hydroxysteroid dehydrogenase deficiency: Difference between revisions
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==Overview== | ==Overview== | ||
3 beta-hydroxysteroid dehydrogenase deficiency is a rare disease of congenital. It is characterized by impaired pathway biosynthesis of [[progestins]], [[mineralocorticoids]], [[glucocorticoids]], and [[androgens]]. As a result of [[cortisol]] absence, [[corticotropin]] ([[ACTH]]) secretion increases and leads to produce 3-hydroxy-delta-5-steroids pregnenolone, [[17-hydroxypregnenolone]], and [[dehydroepiandrosterone]] ([[DHEA]]), also their sulfates. In peripheral tissues the conversion of DHEA sulfate (DHEAS) to testosterone, is responsible for virilization in females. 3 beta-hydroxysteroid dehydrogenase deficiency is caused by a mutation in the HSD3B2 [[gene]]. Symptoms of 3 beta-hydroxysteroid dehydrogenase deficiency may include symptoms of both [[cortisol]] and [[aldosterone]] deficiency such as feeding difficulties, [[vomiting]], [[volume depletion]], [[undervirilization]] in newborn males, and mild [[virilization]] and [[clitoromegaly]] in newborn female. Diagnosis for 3 beta-hydroxysteroid dehydrogenase deficiency is based on delta-5-17-hydroxypregnenolone high levels. The mainstay of therapy for 3 beta-hydroxysteroid dehydrogenase deficiency is [[hydrocortisone]] and [[fludrocortisone acetate]]. The reconstruction surgery for [[ambiguous genitalia]] in genetically male patients may be applied. | |||
==Historical Perspective== | ==Historical Perspective== | ||
3 beta-hydroxysteroid dehydrogenase deficiency first time described in 1962, in a patient with [[ambiguous genitalia]] and salt wasting.<ref name="pmid13968789">{{cite journal |vauthors=BONGIOVANNI AM |title=The adrenogenital syndrome with deficiency of 3 beta-hydroxysteroid dehydrogenase |journal=J. Clin. Invest. |volume=41 |issue= |pages=2086–92 |year=1962 |pmid=13968789 |pmc=291138 |doi=10.1172/JCI104666 |url=}}</ref> | 3 beta-hydroxysteroid dehydrogenase deficiency first time described in 1962, in a patient with [[ambiguous genitalia]] and salt wasting.<ref name="pmid13968789">{{cite journal |vauthors=BONGIOVANNI AM |title=The adrenogenital syndrome with deficiency of 3 beta-hydroxysteroid dehydrogenase |journal=J. Clin. Invest. |volume=41 |issue= |pages=2086–92 |year=1962 |pmid=13968789 |pmc=291138 |doi=10.1172/JCI104666 |url=}}</ref> | ||
==Classification== | ==Classification== | ||
There are two types of 3 beta-hydroxysteroid dehydrogenase deficiency: the salt-wasting, and non-salt-wasting type. | There are two types of 3 beta-hydroxysteroid dehydrogenase deficiency: the salt-wasting, and non-salt-wasting type. | ||
==Pathophysiology== | ==Pathophysiology== | ||
The pathogenesis of 3 beta-hydroxysteroid dehydrogenase deficiency is characterized by impaired pathway biosynthesis of [[progestins]], [[mineralocorticoids]], [[glucocorticoids]], and [[androgens]]. As a result of [[cortisol]] absence, [[corticotropin]] ([[ACTH]]) secretion increases and leads to produce 3-hydroxy-delta-5-steroids pregnenolone, [[17-hydroxypregnenolone]], and [[dehydroepiandrosterone]] ([[DHEA]]), also their sulfates. In peripheral tissues the conversion of DHEA sulfate (DHEAS) to testosterone, is responsible for virilization in females.<ref name="pmid13968789">{{cite journal |vauthors=BONGIOVANNI AM |title=The adrenogenital syndrome with deficiency of 3 beta-hydroxysteroid dehydrogenase |journal=J. Clin. Invest. |volume=41 |issue= |pages=2086–92 |year=1962 |pmid=13968789 |pmc=291138 |doi=10.1172/JCI104666 |url=}}</ref> | The pathogenesis of 3 beta-hydroxysteroid dehydrogenase deficiency is characterized by impaired pathway biosynthesis of [[progestins]], [[mineralocorticoids]], [[glucocorticoids]], and [[androgens]]. As a result of [[cortisol]] absence, [[corticotropin]] ([[ACTH]]) secretion increases and leads to produce 3-hydroxy-delta-5-steroids pregnenolone, [[17-hydroxypregnenolone]], and [[dehydroepiandrosterone]] ([[DHEA]]), also their sulfates. In peripheral tissues the conversion of DHEA sulfate (DHEAS) to testosterone, is responsible for virilization in females.<ref name="pmid13968789">{{cite journal |vauthors=BONGIOVANNI AM |title=The adrenogenital syndrome with deficiency of 3 beta-hydroxysteroid dehydrogenase |journal=J. Clin. Invest. |volume=41 |issue= |pages=2086–92 |year=1962 |pmid=13968789 |pmc=291138 |doi=10.1172/JCI104666 |url=}}</ref> | ||
==Causes== | ==Causes== | ||
3 beta-hydroxysteroid dehydrogenase deficiency is caused by a mutation in the HSD3B2 [[gene]]. | 3 beta-hydroxysteroid dehydrogenase deficiency is caused by a mutation in the HSD3B2 [[gene]]. | ||
==Differentiating 3 beta-hydroxysteroid dehydrogenase deficiency from other Diseases== | ==Differentiating 3 beta-hydroxysteroid dehydrogenase deficiency from other Diseases== | ||
3 beta-hydroxysteroid dehydrogenase deficiency must be differentiated from other diseases that cause [[ambiguous genitalia]] such as: [[21-hydroxylase deficiency]], [[11 beta hydroxylase deficiency|11-β hydroxylase deficiency]], [[17 alpha-hydroxylase deficiency]], gestational [[hyperandrogenism]] and P450-oxidoreductase deficiency. | 3 beta-hydroxysteroid dehydrogenase deficiency must be differentiated from other diseases that cause [[ambiguous genitalia]] such as: [[21-hydroxylase deficiency]], [[11 beta hydroxylase deficiency|11-β hydroxylase deficiency]], [[17 alpha-hydroxylase deficiency]], gestational [[hyperandrogenism]] and P450-oxidoreductase deficiency. | ||
==Epidemiology and Demographics== | ==Epidemiology and Demographics== | ||
The [[prevalence]] of 3 beta-hydroxysteroid dehydrogenase deficiency is unknown. At least 60 affected individuals have been reported.<ref name="url3-beta-hydroxysteroid dehydrogenase deficiency - Genetics Home Reference">{{cite web |url=https://ghr.nlm.nih.gov/condition/3-beta-hydroxysteroid-dehydrogenase-deficiency#statistics |title=3-beta-hydroxysteroid dehydrogenase deficiency - Genetics Home Reference |format= |work= |accessdate=}}</ref> | The [[prevalence]] of 3 beta-hydroxysteroid dehydrogenase deficiency is unknown. At least 60 affected individuals have been reported.<ref name="url3-beta-hydroxysteroid dehydrogenase deficiency - Genetics Home Reference">{{cite web |url=https://ghr.nlm.nih.gov/condition/3-beta-hydroxysteroid-dehydrogenase-deficiency#statistics |title=3-beta-hydroxysteroid dehydrogenase deficiency - Genetics Home Reference |format= |work= |accessdate=}}</ref> | ||
==Risk Factors== | ==Risk Factors== | ||
Common risk factors in the development of 3 beta-hydroxysteroid dehydrogenase deficiency is [[family history]] of this disease. | Common risk factors in the development of 3 beta-hydroxysteroid dehydrogenase deficiency is [[family history]] of this disease. | ||
== Diagnosis == | == Diagnosis == | ||
=== Symptoms === | === Symptoms === | ||
Symptoms of 3 beta-hydroxysteroid dehydrogenase deficiency may include symptoms of both [[cortisol]] and [[aldosterone]] deficiency such as feeding difficulties, [[vomiting]], [[volume depletion]], [[muscle weakness]]; [[undervirilization]] in newborn males, and mild [[virilization]] and [[clitoromegaly]] in newborn female. <ref name="pmid7626445">{{cite journal |vauthors=Simard J, Rheaume E, Mebarki F, Sanchez R, New MI, Morel Y, Labrie F |title=Molecular basis of human 3 beta-hydroxysteroid dehydrogenase deficiency |journal=J. Steroid Biochem. Mol. Biol. |volume=53 |issue=1-6 |pages=127–38 |year=1995 |pmid=7626445 |doi= |url=}}</ref> | Symptoms of 3 beta-hydroxysteroid dehydrogenase deficiency may include symptoms of both [[cortisol]] and [[aldosterone]] deficiency such as feeding difficulties, [[vomiting]], [[volume depletion]], [[muscle weakness]]; [[undervirilization]] in newborn males, and mild [[virilization]] and [[clitoromegaly]] in newborn female. <ref name="pmid7626445">{{cite journal |vauthors=Simard J, Rheaume E, Mebarki F, Sanchez R, New MI, Morel Y, Labrie F |title=Molecular basis of human 3 beta-hydroxysteroid dehydrogenase deficiency |journal=J. Steroid Biochem. Mol. Biol. |volume=53 |issue=1-6 |pages=127–38 |year=1995 |pmid=7626445 |doi= |url=}}</ref> | ||
=== Physical Examination === | === Physical Examination === | ||
Physical examination may be remarkable for: [[undervirilization]] in newborn males and mild [[virilization]] and [[clitoromegaly]] in newborn female. | Physical examination may be remarkable for: [[undervirilization]] in newborn males and mild [[virilization]] and [[clitoromegaly]] in newborn female. | ||
=== Laboratory Findings === | === Laboratory Findings === | ||
Diagnosis for 3 beta-hydroxysteroid dehydrogenase deficiency is based on delta-5-17-hydroxypregnenolone high levels. <ref name="pmid12050224">{{cite journal |vauthors=Lutfallah C, Wang W, Mason JI, Chang YT, Haider A, Rich B, Castro-Magana M, Copeland KC, David R, Pang S |title=Newly proposed hormonal criteria via genotypic proof for type II 3beta-hydroxysteroid dehydrogenase deficiency |journal=J. Clin. Endocrinol. Metab. |volume=87 |issue=6 |pages=2611–22 |year=2002 |pmid=12050224 |doi=10.1210/jcem.87.6.8615 |url=}}</ref> Other laboratory findings include: hyponatremia, hyperkalemia. | Diagnosis for 3 beta-hydroxysteroid dehydrogenase deficiency is based on delta-5-17-hydroxypregnenolone high levels. <ref name="pmid12050224">{{cite journal |vauthors=Lutfallah C, Wang W, Mason JI, Chang YT, Haider A, Rich B, Castro-Magana M, Copeland KC, David R, Pang S |title=Newly proposed hormonal criteria via genotypic proof for type II 3beta-hydroxysteroid dehydrogenase deficiency |journal=J. Clin. Endocrinol. Metab. |volume=87 |issue=6 |pages=2611–22 |year=2002 |pmid=12050224 |doi=10.1210/jcem.87.6.8615 |url=}}</ref> Other laboratory findings include: hyponatremia, hyperkalemia. | ||
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=== Medical Therapy === | === Medical Therapy === | ||
The mainstay of therapy for 3 beta-hydroxysteroid dehydrogenase deficiency is [[hydrocortisone]] and [[fludrocortisone acetate]]. Gender-appropriate replacement of [[androgens]] or [[estrogens]] with [[progestins]] is necessary at the [[puberty]] time. | The mainstay of therapy for 3 beta-hydroxysteroid dehydrogenase deficiency is [[hydrocortisone]] and [[fludrocortisone acetate]]. Gender-appropriate replacement of [[androgens]] or [[estrogens]] with [[progestins]] is necessary at the [[puberty]] time. | ||
=== Surgery === | === Surgery === | ||
The reconstruction surgery for [[ambiguous genitalia]] in genetically male patients may be applied. | The reconstruction surgery for [[ambiguous genitalia]] in genetically male patients may be applied. | ||
==References== | ==References== | ||
{{Reflist|2}} | {{Reflist|2}} | ||
{{WikiDoc Help Menu}} | {{WikiDoc Help Menu}} | ||
{{WikiDoc Sources}} | {{WikiDoc Sources}} | ||
Revision as of 13:59, 9 August 2017
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mehrian Jafarizade, M.D [2]
Overview
3 beta-hydroxysteroid dehydrogenase deficiency is a rare disease of congenital. It is characterized by impaired pathway biosynthesis of progestins, mineralocorticoids, glucocorticoids, and androgens. As a result of cortisol absence, corticotropin (ACTH) secretion increases and leads to produce 3-hydroxy-delta-5-steroids pregnenolone, 17-hydroxypregnenolone, and dehydroepiandrosterone (DHEA), also their sulfates. In peripheral tissues the conversion of DHEA sulfate (DHEAS) to testosterone, is responsible for virilization in females. 3 beta-hydroxysteroid dehydrogenase deficiency is caused by a mutation in the HSD3B2 gene. Symptoms of 3 beta-hydroxysteroid dehydrogenase deficiency may include symptoms of both cortisol and aldosterone deficiency such as feeding difficulties, vomiting, volume depletion, undervirilization in newborn males, and mild virilization and clitoromegaly in newborn female. Diagnosis for 3 beta-hydroxysteroid dehydrogenase deficiency is based on delta-5-17-hydroxypregnenolone high levels. The mainstay of therapy for 3 beta-hydroxysteroid dehydrogenase deficiency is hydrocortisone and fludrocortisone acetate. The reconstruction surgery for ambiguous genitalia in genetically male patients may be applied.
Historical Perspective
3 beta-hydroxysteroid dehydrogenase deficiency first time described in 1962, in a patient with ambiguous genitalia and salt wasting.[1]
Classification
There are two types of 3 beta-hydroxysteroid dehydrogenase deficiency: the salt-wasting, and non-salt-wasting type.
Pathophysiology
The pathogenesis of 3 beta-hydroxysteroid dehydrogenase deficiency is characterized by impaired pathway biosynthesis of progestins, mineralocorticoids, glucocorticoids, and androgens. As a result of cortisol absence, corticotropin (ACTH) secretion increases and leads to produce 3-hydroxy-delta-5-steroids pregnenolone, 17-hydroxypregnenolone, and dehydroepiandrosterone (DHEA), also their sulfates. In peripheral tissues the conversion of DHEA sulfate (DHEAS) to testosterone, is responsible for virilization in females.[1]
Causes
3 beta-hydroxysteroid dehydrogenase deficiency is caused by a mutation in the HSD3B2 gene.
Differentiating 3 beta-hydroxysteroid dehydrogenase deficiency from other Diseases
3 beta-hydroxysteroid dehydrogenase deficiency must be differentiated from other diseases that cause ambiguous genitalia such as: 21-hydroxylase deficiency, 11-β hydroxylase deficiency, 17 alpha-hydroxylase deficiency, gestational hyperandrogenism and P450-oxidoreductase deficiency.
Epidemiology and Demographics
The prevalence of 3 beta-hydroxysteroid dehydrogenase deficiency is unknown. At least 60 affected individuals have been reported.[2]
Risk Factors
Common risk factors in the development of 3 beta-hydroxysteroid dehydrogenase deficiency is family history of this disease.
Diagnosis
Symptoms
Symptoms of 3 beta-hydroxysteroid dehydrogenase deficiency may include symptoms of both cortisol and aldosterone deficiency such as feeding difficulties, vomiting, volume depletion, muscle weakness; undervirilization in newborn males, and mild virilization and clitoromegaly in newborn female. [3]
Physical Examination
Physical examination may be remarkable for: undervirilization in newborn males and mild virilization and clitoromegaly in newborn female.
Laboratory Findings
Diagnosis for 3 beta-hydroxysteroid dehydrogenase deficiency is based on delta-5-17-hydroxypregnenolone high levels. [4] Other laboratory findings include: hyponatremia, hyperkalemia.
Treatment
Medical Therapy
The mainstay of therapy for 3 beta-hydroxysteroid dehydrogenase deficiency is hydrocortisone and fludrocortisone acetate. Gender-appropriate replacement of androgens or estrogens with progestins is necessary at the puberty time.
Surgery
The reconstruction surgery for ambiguous genitalia in genetically male patients may be applied.
References
- ↑ 1.0 1.1 BONGIOVANNI AM (1962). "The adrenogenital syndrome with deficiency of 3 beta-hydroxysteroid dehydrogenase". J. Clin. Invest. 41: 2086–92. doi:10.1172/JCI104666. PMC 291138. PMID 13968789.
- ↑ "3-beta-hydroxysteroid dehydrogenase deficiency - Genetics Home Reference".
- ↑ Simard J, Rheaume E, Mebarki F, Sanchez R, New MI, Morel Y, Labrie F (1995). "Molecular basis of human 3 beta-hydroxysteroid dehydrogenase deficiency". J. Steroid Biochem. Mol. Biol. 53 (1–6): 127–38. PMID 7626445.
- ↑ Lutfallah C, Wang W, Mason JI, Chang YT, Haider A, Rich B, Castro-Magana M, Copeland KC, David R, Pang S (2002). "Newly proposed hormonal criteria via genotypic proof for type II 3beta-hydroxysteroid dehydrogenase deficiency". J. Clin. Endocrinol. Metab. 87 (6): 2611–22. doi:10.1210/jcem.87.6.8615. PMID 12050224.