Inborn errors of steroid metabolism

Inborn error of steroid metabolism
	Steroidogenesis

An inborn error of steroid metabolism is an inborn error of metabolism due to defects in steroid metabolism.^{[citation needed]}

Types

A variety of conditions of abnormal steroidogenesis exist due to genetic mutations in the steroidogenic enzymes involved in the process, of which include:

Generalized

20,22-Desmolase (P450scc) deficiency: blocks production of all steroid hormones from cholesterol
3β-Hydroxysteroid dehydrogenase 2 deficiency: impairs progestogen and androgen metabolism; prevents the synthesis of estrogens, glucocorticoids, and mineralocorticoids; causes androgen deficiency in males and androgen excess in females
Combined 17α-hydroxylase/17,20-lyase deficiency: impairs progestogen metabolism; prevents androgen, estrogen, and glucocorticoid synthesis; causes mineralocorticoid excess
Cytochrome P450 oxidoreductase deficiency: prevents production of numerous but not all sex steroids,^[1] as well as other metabolic reactions

Androgen- and estrogen-specific

Isolated 17,20-lyase deficiency: prevents androgen and estrogen synthesis.^[2]
- Cytochrome b₅ deficiency: subtype of isolated 17,20-lyase deficiency; additionally results in elevated methemoglobin and/or methemoglobinemia
17β-Hydroxysteroid dehydrogenase 3 deficiency: impairs androgen and estrogen metabolism; results in androgen deficiency in males and androgen excess and estrogen deficiency in females
5α-Reductase 2 deficiency: prevents the conversion of testosterone to dihydrotestosterone; causes androgen deficiency in males
Aromatase deficiency: prevents estrogen synthesis; causes androgen excess in females
Aromatase excess: causes excessive conversion of androgens to estrogens; results in estrogen excess in both sexes and androgen deficiency in males.

Glucocorticoid- and mineralocorticoid-specific

21-Hydroxylase deficiency: prevents glucocorticoid and mineralocorticoid synthesis; causes androgen excess in females
11β-Hydroxylase 1 deficiency: impairs glucocorticoid and mineralocorticoid metabolism; causes glucocorticoid deficiency and mineralocorticoid excess as well as androgen excess in females
11β-Hydroxylase 2 deficiency: impairs corticosteroid metabolism; results in excessive mineralocorticoid activity
18-Hydroxylase deficiency: prevents mineralocorticoid synthesis; results in mineralocorticoid deficiency
18-Hydroxylase overactivity: impairs mineralocorticoid metabolism; results in mineralocorticoid excess

Miscellaneous

In addition, several conditions of abnormal steroidogenesis due to genetic mutations in receptors, as opposed to enzymes, also exist, including:^{[citation needed]}

Gonadotropin-releasing hormone (GnRH) insensitivity: prevents synthesis of sex steroids by the gonads in both sexes
Follicle-stimulating (FSH) hormone insensitivity: prevents synthesis of sex steroids by the gonads in females; merely causes problems with fertility in males
Luteinizing hormone (LH) insensitivity: prevents synthesis of sex steroids by the gonads in males; merely causes problems with fertility in females
Luteinizing hormone (LH) oversensitivity: causes androgen excess in males, resulting in precocious puberty; females are asymptomatic

No activating mutations of the GnRH receptor in humans have been described in the medical literature,^[3] and only one of the FSH receptor has been described, which presented as asymptomatic.^[4]^[5]

References

↑ Parween, Shaheena; Fernández-Cancio, Mónica; Benito-Sanz, Sara; Camats, Núria; Rojas Velazquez, Maria Natalia; López-Siguero, Juan-Pedro; Udhane, Sameer S; Kagawa, Norio et al. (April 2020). "Molecular Basis of CYP19A1 Deficiency in a 46,XX Patient With R550W Mutation in POR: Expanding the PORD Phenotype". The Journal of Clinical Endocrinology & Metabolism 105 (4): e1272–e1290. doi:10.1210/clinem/dgaa076. PMID 32060549.
↑ Fernández-Cancio, Mónica; Camats, Núria; Flück, Christa E.; Zalewski, Adam; Dick, Bernhard; Frey, Brigitte M.; Monné, Raquel; Torán, Núria et al. (2018-04-29). "Mechanism of the Dual Activities of Human CYP17A1 and Binding to Anti-Prostate Cancer Drug Abiraterone Revealed by a Novel V366M Mutation Causing 17,20 Lyase Deficiency" (in en). Pharmaceuticals 11 (2): 37. doi:10.3390/ph11020037. PMID 29710837.
↑ "Clinical and molecular genetics of the human GnRH receptor". Human Reproduction Update 9 (6): 523–30. 2003. doi:10.1093/humupd/dmg040. PMID 14714589.
↑ Eberhard Nieschlag; Hermann M. Behre; Susan Nieschlag (3 December 2009). Andrology: Male Reproductive Health and Dysfunction. Springer. p. 226. ISBN 978-3-540-78354-1. https://books.google.com/books?id=mEgckDNkonUC&pg=PA226. Retrieved 11 June 2012.
↑ Mark A. Sperling (25 April 2008). Pediatric Endocrinology E-Book. Elsevier Health Sciences. p. 35. ISBN 978-1-4377-1109-7. https://books.google.com/books?id=WIus0AIUhWIC&pg=PA35. Retrieved 11 June 2012.

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[1] Parween, Shaheena; Fernández-Cancio, Mónica; Benito-Sanz, Sara; Camats, Núria; Rojas Velazquez, Maria Natalia; López-Siguero, Juan-Pedro; Udhane, Sameer S; Kagawa, Norio et al. (April 2020). "Molecular Basis of CYP19A1 Deficiency in a 46,XX Patient With R550W Mutation in POR: Expanding the PORD Phenotype". The Journal of Clinical Endocrinology & Metabolism 105 (4): e1272–e1290. doi:10.1210/clinem/dgaa076. PMID 32060549.

[2] Fernández-Cancio, Mónica; Camats, Núria; Flück, Christa E.; Zalewski, Adam; Dick, Bernhard; Frey, Brigitte M.; Monné, Raquel; Torán, Núria et al. (2018-04-29). "Mechanism of the Dual Activities of Human CYP17A1 and Binding to Anti-Prostate Cancer Drug Abiraterone Revealed by a Novel V366M Mutation Causing 17,20 Lyase Deficiency" (in en). Pharmaceuticals 11 (2): 37. doi:10.3390/ph11020037. PMID 29710837.

[pmid14714589-3] "Clinical and molecular genetics of the human GnRH receptor". Human Reproduction Update 9 (6): 523–30. 2003. doi:10.1093/humupd/dmg040. PMID 14714589.

[NieschlagBehre2009-4] Eberhard Nieschlag; Hermann M. Behre; Susan Nieschlag (3 December 2009). Andrology: Male Reproductive Health and Dysfunction. Springer. p. 226. ISBN 978-3-540-78354-1. https://books.google.com/books?id=mEgckDNkonUC&pg=PA226. Retrieved 11 June 2012.

[Sperling2008-5] Mark A. Sperling (25 April 2008). Pediatric Endocrinology E-Book. Elsevier Health Sciences. p. 35. ISBN 978-1-4377-1109-7. https://books.google.com/books?id=WIus0AIUhWIC&pg=PA35. Retrieved 11 June 2012.

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Inborn errors of steroid metabolism

Topic: Medicine

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