Cytochrome P450-oxidoreductase (POR) deficiency (ORD): Difference between revisions
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==Overview== | ==Overview== | ||
Cytochrome P450-oxidoreductase (POR) deficiency is a type of [[congenital adrenal hyperplasia]] that caused by mutations in the [[flavoprotein]] co-factor of the enzymes [[CYP17A1]], [[CYP21A2]], and [[CYP19A1]] ([[aromatase]]). Severe [[Undervirilization]] in boys and severe [[virilization]] in girls and [[Antley-Bixler syndrome]] of [[craniofacial malformations]] are clinical finding of | Cytochrome P450-oxidoreductase (POR) deficiency is a type of [[congenital adrenal hyperplasia]] that caused by [[mutations]] in the [[flavoprotein]] co-factor of the [[enzymes]] [[CYP17A1]], [[CYP21A2]], and [[CYP19A1]] ([[aromatase]]). Severe [[Undervirilization]] in boys and severe [[virilization]] in girls and [[Antley-Bixler syndrome]] of [[craniofacial malformations]] are clinical finding of cytocrome P450-oxidoreductase deficiency. The mainstay of therapy for cytochrome P450-oxidoreductase deficiency is [[hydrocortisone]] to replace [[glucocorticoid]] deficiency. | ||
==Historical Perspective== | ==Historical Perspective== | ||
[[ | In 1865, Luigi De Crecchio, an Italian [[pathologist]] was the first who discovered [[Congenital adrenal hyperplasia]].<ref name="pmid25635623">{{cite journal |vauthors=Delle Piane L, Rinaudo PF, Miller WL |title=150 years of congenital adrenal hyperplasia: translation and commentary of De Crecchio's classic paper from 1865 |journal=Endocrinology |volume=156 |issue=4 |pages=1210–7 |year=2015 |pmid=25635623 |doi=10.1210/en.2014-1879 |url=}}</ref> | ||
==Classification== | ==Classification== | ||
There is no established classification system for cytochrome P450-oxidoreductase deficiency. | There is no established classification system for cytochrome P450-oxidoreductase deficiency. | ||
==Pathophysiology== | ==Pathophysiology== | ||
The cytochrome P450 oxidoreductase (POR) enzyme serves as an [[electron donor]] enzyme for many enzymes such as [[steroid]] synthesis enzymes [[CYP17A1]], [[CYP21A2]]. | The cytochrome P450 oxidoreductase (POR) enzyme serves as an [[electron donor]] enzyme for many [[enzymes]] such as [[steroid]] synthesis enzymes [[CYP17A1]], and [[CYP21A2]]. Cytochrome P450-oxidoreductase deficiency is characterized by combined [[CYP17A1]] and [[CYP21A2]] deficiency. | ||
* [[CYP17A1]] encodes[[17α-hydroxylase]]/17,20α-hydroxylase, a [[cytochrome P450]] enzyme which acts upon: | |||
** [[Pregnenolone]] and [[progesterone]] to add a [[hydroxyl]] (-OH) group at [[carbon]] 17 of the steroid D ring (the [[hydroxylase]] activity). | |||
** [[17-Hydroxyprogesterone|17-hydroxyprogesterone]] and [[17-Hydroxypregnenolone|17-hydroxypregnenolone]] to split the side chain off the [[steroid]] [[nucleus]]. | |||
* [[CYP21A2]] encodes steroid 21-hydroxylase, a [[cytochrome P450]] [[enzyme]] which is involved with the [[biosynthesis]] of the [[Steroid hormone|steroid hormones]] [[aldosterone]] and [[cortisol]]. | |||
Also, cytochrome P450 oxidoreductase enzyme serves as a co-factor for an enzyme called [[lanosterol]] de-methylase ([[CYP51A1]]), which is effective in de novo [[cholesterol]] synthesis. In this disease [[cholesterol]] loss may lead to [[craniofacial malformations]] and [[Antley-Bixler syndrome]] (ABS).<ref name="pmid19258400">{{cite journal |vauthors=Fukami M, Nishimura G, Homma K, Nagai T, Hanaki K, Uematsu A, Ishii T, Numakura C, Sawada H, Nakacho M, Kowase T, Motomura K, Haruna H, Nakamura M, Ohishi A, Adachi M, Tajima T, Hasegawa Y, Hasegawa T, Horikawa R, Fujieda K, Ogata T |title=Cytochrome P450 oxidoreductase deficiency: identification and characterization of biallelic mutations and genotype-phenotype correlations in 35 Japanese patients |journal=J. Clin. Endocrinol. Metab. |volume=94 |issue=5 |pages=1723–31 |year=2009 |pmid=19258400 |doi=10.1210/jc.2008-2816 |url=}}</ref><ref name="pmid2932643">{{cite journal |vauthors=Peterson RE, Imperato-McGinley J, Gautier T, Shackleton C |title=Male pseudohermaphroditism due to multiple defects in steroid-biosynthetic microsomal mixed-function oxidases. A new variant of congenital adrenal hyperplasia |journal=N. Engl. J. Med. |volume=313 |issue=19 |pages=1182–91 |year=1985 |pmid=2932643 |doi=10.1056/NEJM198511073131903 |url=}}</ref><ref name="pmid15793702">{{cite journal |vauthors=Huang N, Pandey AV, Agrawal V, Reardon W, Lapunzina PD, Mowat D, Jabs EW, Van Vliet G, Sack J, Flück CE, Miller WL |title=Diversity and function of mutations in p450 oxidoreductase in patients with Antley-Bixler syndrome and disordered steroidogenesis |journal=Am. J. Hum. Genet. |volume=76 |issue=5 |pages=729–49 |year=2005 |pmid=15793702 |pmc=1199364 |doi=10.1086/429417 |url=}}</ref><ref name="pmid12116245">{{cite journal |vauthors=Kelley RI, Kratz LE, Glaser RL, Netzloff ML, Wolf LM, Jabs EW |title=Abnormal sterol metabolism in a patient with Antley-Bixler syndrome and ambiguous genitalia |journal=Am. J. Med. Genet. |volume=110 |issue=2 |pages=95–102 |year=2002 |pmid=12116245 |doi=10.1002/ajmg.10510 |url=}}</ref><ref name="pmid15189162">{{cite journal |vauthors=Mann RK, Beachy PA |title=Novel lipid modifications of secreted protein signals |journal=Annu. Rev. Biochem. |volume=73 |issue= |pages=891–923 |year=2004 |pmid=15189162 |doi=10.1146/annurev.biochem.73.011303.073933 |url=}}</ref> | |||
==Causes== | ==Causes== | ||
Cytochrome P450-oxidoreductase (POR) deficiency is caused by [[mutations]] in the [[flavoprotein]] co-factor of the enzymes [[CYP17A1]], [[CYP21A2]], and [[CYP19A1]] ([[aromatase]]). | Cytochrome P450-oxidoreductase (POR) deficiency is caused by [[mutations]] in the [[flavoprotein]] that is a co-factor of the enzymes [[CYP17A1]], [[CYP21A2]], and [[CYP19A1]] ([[aromatase]]). | ||
==Differentiating [disease name] from other Diseases== | ==Differentiating [disease name] from other Diseases== | ||
Cytochrome P450-oxidoreductase 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]]. | Cytochrome P450-oxidoreductase 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]], and gestational [[hyperandrogenism]]. | ||
{| class="wikitable" | |||
! rowspan="2" align="center" style="background:#4479BA; color: #FFFFFF;" + |Disease name | |||
! colspan="2" align="center" style="background:#4479BA; color: #FFFFFF;" + |Steroid status | |||
! rowspan="2" align="center" style="background:#4479BA; color: #FFFFFF;" + |Important clinical findings | |||
|- | |||
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Increased | |||
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Decreased | |||
|- | |||
![[21-hydroxylase deficiency|Classic type of 21-hydroxylase deficiency]] | |||
| | |||
* [[17-Hydroxyprogesterone|17-hydroxyprogesterone]] | |||
* [[Progesterone]] | |||
* [[Androstenedione]] | |||
* [[DHEA]] | |||
| | |||
* [[Aldosterone]] | |||
* [[Corticosterone]] (salt-wasting) | |||
* [[Cortisol]] ([[virilization]]) | |||
| | |||
* [[Ambiguous genitalia]] in female | |||
* [[Virilization]] in female | |||
* Salt-wasting | |||
* [[Hypotension]] and [[hyperkalemia]] | |||
|- | |||
![[11β-hydroxylase deficiency|11-β hydroxylase deficiency]] | |||
| | |||
* [[Deoxycorticosterone]] | |||
* 11-Deoxy-[[cortisol]] | |||
* [[17-Hydroxyprogesterone|17-hydroxyprogesterone]] (mild elevation) | |||
| | |||
* [[Cortisol]] | |||
* [[Corticosterone]] | |||
* [[Aldosterone]] | |||
| | |||
* [[Ambiguous genitalia]] in female | |||
* [[Hypertension]] and [[hypokalemia]] | |||
* [[Virilization]] | |||
|- | |||
![[17 alpha-hydroxylase deficiency|17-α hydroxylase deficiency]] | |||
| | |||
* [[Deoxycorticosterone]] | |||
* [[Corticosterone]] | |||
* [[Progesterone]] | |||
| | |||
* [[Cortisol]] | |||
* [[Aldosterone]] | |||
| | |||
* [[Ambiguous genitalia]] in male | |||
* [[Hypertension]] | |||
* [[Primary amenorrhea]] | |||
* Absence of [[secondary sexual characteristics]] | |||
* Minimal [[body hair]] | |||
|- | |||
![[3 beta-hydroxysteroid dehydrogenase deficiency]] | |||
| | |||
* [[Dehydroepiandrosterone]] | |||
* [[17-hydroxypregnenolone]] | |||
* [[Pregnenolone]] | |||
| | |||
* [[Cortisol]] | |||
* [[Aldosterone]] | |||
| | |||
* [[Vomiting]], [[volume depletion]], [[hyponatremia]], and [[hyperkalemia]] | |||
* 46-XY infants often show [[undervirilization]], due to a block in [[testosterone]] synthesis | |||
|- | |||
! Gestational [[hyperandrogenism]] | |||
| colspan="2" | | |||
* Maternal serum [[androgen]] concentrations (usually [[testosterone]] and [[androstenedione]]) are high | |||
* If [[virilization]] is caused by exogenous hormone administration, the values may be low because the offending hormone is usually a synthetic [[steroid]] not measured in assays for [[testosterone]] or other [[androgens]] | |||
| | |||
* [[Androgen]] excess in mother | |||
* History of [[androgen]] containing [[medication]] consumption during [[pregnancy]] in mother | |||
* [[Virilization]] in a 46,XX individual with normal female internal anatomy | |||
* Causes include maternal [[luteoma]] or theca-[[lutein]] [[cysts]], and [[placental]] [[aromatase]] enzyme deficiency | |||
|} | |||
==Epidemiology and Demographics== | ==Epidemiology and Demographics== | ||
Cytochrome P450-oxidoreductase (POR) deficiency is a | Cytochrome P450-oxidoreductase (POR) deficiency is a rere disease with unknown [[prevalence]].<ref name="pmid14758361">{{cite journal |vauthors=Flück CE, Tajima T, Pandey AV, Arlt W, Okuhara K, Verge CF, Jabs EW, Mendonça BB, Fujieda K, Miller WL |title=Mutant P450 oxidoreductase causes disordered steroidogenesis with and without Antley-Bixler syndrome |journal=Nat. Genet. |volume=36 |issue=3 |pages=228–30 |year=2004 |pmid=14758361 |doi=10.1038/ng1300 |url=}}</ref><ref name="pmid18559916">{{cite journal |vauthors=Hershkovitz E, Parvari R, Wudy SA, Hartmann MF, Gomes LG, Loewental N, Miller WL |title=Homozygous mutation G539R in the gene for P450 oxidoreductase in a family previously diagnosed as having 17,20-lyase deficiency |journal=J. Clin. Endocrinol. Metab. |volume=93 |issue=9 |pages=3584–8 |year=2008 |pmid=18559916 |pmc=2567854 |doi=10.1210/jc.2008-0051 |url=}}</ref> | ||
== Diagnosis == | == Diagnosis == | ||
=== Symptoms and physical Examination === | === Symptoms and physical Examination === | ||
*Severe [[Undervirilization]] in boys and severe [[virilization]] in girls but [[pubertal]] development in this disease is not studied enough. | *Severe [[Undervirilization]] in boys and severe [[virilization]] in girls but [[pubertal]] development in this disease is not studied enough. | ||
*[[Antley-Bixler syndrome]] (ABS): [[craniofacial malformations]] (midface [[hypoplasia]] with low set ears and pear-shaped nose, [[arachnodactyly]], [[clinodactyly]], and radio-humeral [[synostosis]].<ref name="pmid2932643">{{cite journal |vauthors=Peterson RE, Imperato-McGinley J, Gautier T, Shackleton C |title=Male pseudohermaphroditism due to multiple defects in steroid-biosynthetic microsomal mixed-function oxidases. A new variant of congenital adrenal hyperplasia |journal=N. Engl. J. Med. |volume=313 |issue=19 |pages=1182–91 |year=1985 |pmid=2932643 |doi=10.1056/NEJM198511073131903 |url=}}</ref><ref name="pmid15793702">{{cite journal |vauthors=Huang N, Pandey AV, Agrawal V, Reardon W, Lapunzina PD, Mowat D, Jabs EW, Van Vliet G, Sack J, Flück CE, Miller WL |title=Diversity and function of mutations in p450 oxidoreductase in patients with Antley-Bixler syndrome and disordered steroidogenesis |journal=Am. J. Hum. Genet. |volume=76 |issue=5 |pages=729–49 |year=2005 |pmid=15793702 |pmc=1199364 |doi=10.1086/429417 |url=}}</ref><ref name="pmid12116245">{{cite journal |vauthors=Kelley RI, Kratz LE, Glaser RL, Netzloff ML, Wolf LM, Jabs EW |title=Abnormal sterol metabolism in a patient with Antley-Bixler syndrome and ambiguous genitalia |journal=Am. J. Med. Genet. |volume=110 |issue=2 |pages=95–102 |year=2002 |pmid=12116245 |doi=10.1002/ajmg.10510 |url=}}</ref><ref name="pmid15189162">{{cite journal |vauthors=Mann RK, Beachy PA |title=Novel lipid modifications of secreted protein signals |journal=Annu. Rev. Biochem. |volume=73 |issue= |pages=891–923 |year=2004 |pmid=15189162 |doi=10.1146/annurev.biochem.73.011303.073933 |url=}}</ref> | *[[Antley-Bixler syndrome]] (ABS): [[craniofacial malformations]] (midface [[hypoplasia]] with low set ears and pear-shaped nose), [[arachnodactyly]], [[clinodactyly]], and radio-humeral [[synostosis]].<ref name="pmid2932643">{{cite journal |vauthors=Peterson RE, Imperato-McGinley J, Gautier T, Shackleton C |title=Male pseudohermaphroditism due to multiple defects in steroid-biosynthetic microsomal mixed-function oxidases. A new variant of congenital adrenal hyperplasia |journal=N. Engl. J. Med. |volume=313 |issue=19 |pages=1182–91 |year=1985 |pmid=2932643 |doi=10.1056/NEJM198511073131903 |url=}}</ref><ref name="pmid15793702">{{cite journal |vauthors=Huang N, Pandey AV, Agrawal V, Reardon W, Lapunzina PD, Mowat D, Jabs EW, Van Vliet G, Sack J, Flück CE, Miller WL |title=Diversity and function of mutations in p450 oxidoreductase in patients with Antley-Bixler syndrome and disordered steroidogenesis |journal=Am. J. Hum. Genet. |volume=76 |issue=5 |pages=729–49 |year=2005 |pmid=15793702 |pmc=1199364 |doi=10.1086/429417 |url=}}</ref><ref name="pmid12116245">{{cite journal |vauthors=Kelley RI, Kratz LE, Glaser RL, Netzloff ML, Wolf LM, Jabs EW |title=Abnormal sterol metabolism in a patient with Antley-Bixler syndrome and ambiguous genitalia |journal=Am. J. Med. Genet. |volume=110 |issue=2 |pages=95–102 |year=2002 |pmid=12116245 |doi=10.1002/ajmg.10510 |url=}}</ref><ref name="pmid15189162">{{cite journal |vauthors=Mann RK, Beachy PA |title=Novel lipid modifications of secreted protein signals |journal=Annu. Rev. Biochem. |volume=73 |issue= |pages=891–923 |year=2004 |pmid=15189162 |doi=10.1146/annurev.biochem.73.011303.073933 |url=}}</ref> | ||
=== Laboratory Findings === | === Laboratory Findings === | ||
[[Genetic testing]] is the gold standard of diagnosis. [[Pregnenolone]], [[progesterone]] and [[17-Hydroxyprogesterone|17-hydroxyprogesterone]] metabolites are increased and [[androgen]] metabolites are decreased.<ref name="pmid15216541">{{cite journal |vauthors=Shackleton C, Marcos J, Malunowicz EM, Szarras-Czapnik M, Jira P, Taylor NF, Murphy N, Crushell E, Gottschalk M, Hauffa B, Cragun DL, Hopkin RJ, Adachi M, Arlt W |title=Biochemical diagnosis of Antley-Bixler syndrome by steroid analysis |journal=Am. J. Med. Genet. A |volume=128A |issue=3 |pages=223–31 |year=2004 |pmid=15216541 |doi=10.1002/ajmg.a.30104 |url=}}</ref> | [[Genetic testing]] is the gold standard of diagnosis. [[Pregnenolone]], [[progesterone]] and [[17-Hydroxyprogesterone|17-hydroxyprogesterone]] metabolites are increased and [[androgen]] [[metabolites]] are decreased.<ref name="pmid15216541">{{cite journal |vauthors=Shackleton C, Marcos J, Malunowicz EM, Szarras-Czapnik M, Jira P, Taylor NF, Murphy N, Crushell E, Gottschalk M, Hauffa B, Cragun DL, Hopkin RJ, Adachi M, Arlt W |title=Biochemical diagnosis of Antley-Bixler syndrome by steroid analysis |journal=Am. J. Med. Genet. A |volume=128A |issue=3 |pages=223–31 |year=2004 |pmid=15216541 |doi=10.1002/ajmg.a.30104 |url=}}</ref> | ||
==Treatment== | ==Treatment== | ||
=== Medical Therapy === | === Medical Therapy === | ||
The mainstay of therapy for cytochrome P450-oxidoreductase deficiency is [[hydrocortisone]] to replace [[glucocorticoid]] deficiency. Gender-appropriate replacement of [[androgens]] or [[estrogens]] with [[progestins]] is necessary at the [[puberty]] time. | The mainstay of therapy for cytochrome P450-oxidoreductase deficiency is [[hydrocortisone]] to replace [[glucocorticoid]] deficiency. Gender-appropriate replacement of [[androgens]] or [[estrogens]] with [[progestins]] is necessary at the [[puberty]] time. | ||
* Preferred regiemen: [[hydrocortisone]] oral, 15 to 25 mg/day in 2 to 3 divided doses. | |||
=== Surgery === | === Surgery === | ||
The reconstruction surgery for [[ambiguous genitalia]] in [[genetically]] male patients may be applied.<ref name="pmid11344932">{{cite journal |vauthors=Schnitzer JJ, Donahoe PK |title=Surgical treatment of congenital adrenal hyperplasia |journal=Endocrinol. Metab. Clin. North Am. |volume=30 |issue=1 |pages=137–54 |year=2001 |pmid=11344932 |doi= |url=}}</ref> | The reconstruction surgery for [[ambiguous genitalia]] in [[genetically]] male patients may be applied.<ref name="pmid11344932">{{cite journal |vauthors=Schnitzer JJ, Donahoe PK |title=Surgical treatment of congenital adrenal hyperplasia |journal=Endocrinol. Metab. Clin. North Am. |volume=30 |issue=1 |pages=137–54 |year=2001 |pmid=11344932 |doi= |url=}}</ref> | ||
Latest revision as of 17:52, 17 October 2017
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mehrian Jafarizade, M.D [2]
Synonyms and keywords: ORD, POR deficiency, P450-oxidoreductase cytochrome deficiency
Overview
Cytochrome P450-oxidoreductase (POR) deficiency is a type of congenital adrenal hyperplasia that caused by mutations in the flavoprotein co-factor of the enzymes CYP17A1, CYP21A2, and CYP19A1 (aromatase). Severe Undervirilization in boys and severe virilization in girls and Antley-Bixler syndrome of craniofacial malformations are clinical finding of cytocrome P450-oxidoreductase deficiency. The mainstay of therapy for cytochrome P450-oxidoreductase deficiency is hydrocortisone to replace glucocorticoid deficiency.
Historical Perspective
In 1865, Luigi De Crecchio, an Italian pathologist was the first who discovered Congenital adrenal hyperplasia.[1]
Classification
There is no established classification system for cytochrome P450-oxidoreductase deficiency.
Pathophysiology
The cytochrome P450 oxidoreductase (POR) enzyme serves as an electron donor enzyme for many enzymes such as steroid synthesis enzymes CYP17A1, and CYP21A2. Cytochrome P450-oxidoreductase deficiency is characterized by combined CYP17A1 and CYP21A2 deficiency.
- CYP17A1 encodes17α-hydroxylase/17,20α-hydroxylase, a cytochrome P450 enzyme which acts upon:
- Pregnenolone and progesterone to add a hydroxyl (-OH) group at carbon 17 of the steroid D ring (the hydroxylase activity).
- 17-hydroxyprogesterone and 17-hydroxypregnenolone to split the side chain off the steroid nucleus.
- CYP21A2 encodes steroid 21-hydroxylase, a cytochrome P450 enzyme which is involved with the biosynthesis of the steroid hormones aldosterone and cortisol.
Also, cytochrome P450 oxidoreductase enzyme serves as a co-factor for an enzyme called lanosterol de-methylase (CYP51A1), which is effective in de novo cholesterol synthesis. In this disease cholesterol loss may lead to craniofacial malformations and Antley-Bixler syndrome (ABS).[2][3][4][5][6]
Causes
Cytochrome P450-oxidoreductase (POR) deficiency is caused by mutations in the flavoprotein that is a co-factor of the enzymes CYP17A1, CYP21A2, and CYP19A1 (aromatase).
Differentiating [disease name] from other Diseases
Cytochrome P450-oxidoreductase deficiency must be differentiated from other diseases that cause ambiguous genitalia such as: 21-hydroxylase deficiency, 11-β hydroxylase deficiency, 17 alpha-hydroxylase deficiency, and gestational hyperandrogenism.
| Disease name | Steroid status | Important clinical findings | |
|---|---|---|---|
| Increased | Decreased | ||
| Classic type of 21-hydroxylase deficiency |
|
| |
| 11-β hydroxylase deficiency |
|
| |
| 17-α hydroxylase deficiency |
| ||
| 3 beta-hydroxysteroid dehydrogenase deficiency |
| ||
| Gestational hyperandrogenism |
|
| |
Epidemiology and Demographics
Cytochrome P450-oxidoreductase (POR) deficiency is a rere disease with unknown prevalence.[7][8]
Diagnosis
Symptoms and physical Examination
- Severe Undervirilization in boys and severe virilization in girls but pubertal development in this disease is not studied enough.
- Antley-Bixler syndrome (ABS): craniofacial malformations (midface hypoplasia with low set ears and pear-shaped nose), arachnodactyly, clinodactyly, and radio-humeral synostosis.[3][4][5][6]
Laboratory Findings
Genetic testing is the gold standard of diagnosis. Pregnenolone, progesterone and 17-hydroxyprogesterone metabolites are increased and androgen metabolites are decreased.[9]
Treatment
Medical Therapy
The mainstay of therapy for cytochrome P450-oxidoreductase deficiency is hydrocortisone to replace glucocorticoid deficiency. Gender-appropriate replacement of androgens or estrogens with progestins is necessary at the puberty time.
- Preferred regiemen: hydrocortisone oral, 15 to 25 mg/day in 2 to 3 divided doses.
Surgery
The reconstruction surgery for ambiguous genitalia in genetically male patients may be applied.[10]
References
- ↑ Delle Piane L, Rinaudo PF, Miller WL (2015). "150 years of congenital adrenal hyperplasia: translation and commentary of De Crecchio's classic paper from 1865". Endocrinology. 156 (4): 1210–7. doi:10.1210/en.2014-1879. PMID 25635623.
- ↑ Fukami M, Nishimura G, Homma K, Nagai T, Hanaki K, Uematsu A, Ishii T, Numakura C, Sawada H, Nakacho M, Kowase T, Motomura K, Haruna H, Nakamura M, Ohishi A, Adachi M, Tajima T, Hasegawa Y, Hasegawa T, Horikawa R, Fujieda K, Ogata T (2009). "Cytochrome P450 oxidoreductase deficiency: identification and characterization of biallelic mutations and genotype-phenotype correlations in 35 Japanese patients". J. Clin. Endocrinol. Metab. 94 (5): 1723–31. doi:10.1210/jc.2008-2816. PMID 19258400.
- ↑ 3.0 3.1 Peterson RE, Imperato-McGinley J, Gautier T, Shackleton C (1985). "Male pseudohermaphroditism due to multiple defects in steroid-biosynthetic microsomal mixed-function oxidases. A new variant of congenital adrenal hyperplasia". N. Engl. J. Med. 313 (19): 1182–91. doi:10.1056/NEJM198511073131903. PMID 2932643.
- ↑ 4.0 4.1 Huang N, Pandey AV, Agrawal V, Reardon W, Lapunzina PD, Mowat D, Jabs EW, Van Vliet G, Sack J, Flück CE, Miller WL (2005). "Diversity and function of mutations in p450 oxidoreductase in patients with Antley-Bixler syndrome and disordered steroidogenesis". Am. J. Hum. Genet. 76 (5): 729–49. doi:10.1086/429417. PMC 1199364. PMID 15793702.
- ↑ 5.0 5.1 Kelley RI, Kratz LE, Glaser RL, Netzloff ML, Wolf LM, Jabs EW (2002). "Abnormal sterol metabolism in a patient with Antley-Bixler syndrome and ambiguous genitalia". Am. J. Med. Genet. 110 (2): 95–102. doi:10.1002/ajmg.10510. PMID 12116245.
- ↑ 6.0 6.1 Mann RK, Beachy PA (2004). "Novel lipid modifications of secreted protein signals". Annu. Rev. Biochem. 73: 891–923. doi:10.1146/annurev.biochem.73.011303.073933. PMID 15189162.
- ↑ Flück CE, Tajima T, Pandey AV, Arlt W, Okuhara K, Verge CF, Jabs EW, Mendonça BB, Fujieda K, Miller WL (2004). "Mutant P450 oxidoreductase causes disordered steroidogenesis with and without Antley-Bixler syndrome". Nat. Genet. 36 (3): 228–30. doi:10.1038/ng1300. PMID 14758361.
- ↑ Hershkovitz E, Parvari R, Wudy SA, Hartmann MF, Gomes LG, Loewental N, Miller WL (2008). "Homozygous mutation G539R in the gene for P450 oxidoreductase in a family previously diagnosed as having 17,20-lyase deficiency". J. Clin. Endocrinol. Metab. 93 (9): 3584–8. doi:10.1210/jc.2008-0051. PMC 2567854. PMID 18559916.
- ↑ Shackleton C, Marcos J, Malunowicz EM, Szarras-Czapnik M, Jira P, Taylor NF, Murphy N, Crushell E, Gottschalk M, Hauffa B, Cragun DL, Hopkin RJ, Adachi M, Arlt W (2004). "Biochemical diagnosis of Antley-Bixler syndrome by steroid analysis". Am. J. Med. Genet. A. 128A (3): 223–31. doi:10.1002/ajmg.a.30104. PMID 15216541.
- ↑ Schnitzer JJ, Donahoe PK (2001). "Surgical treatment of congenital adrenal hyperplasia". Endocrinol. Metab. Clin. North Am. 30 (1): 137–54. PMID 11344932.