Inborn errors of steroid metabolism

Medical condition

Inborn error of steroid metabolism

Steroidogenesis
Specialty| Medical genetics, endocrinology

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

## Types

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

### Generalized

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* 20,22-Desmolase (P450scc) deficiency: blocks production of all steroid hormones from cholesterol [citation needed]
* 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[citation needed]
* Combined 17α-hydroxylase/17,20-lyase deficiency: impairs progestogen metabolism; prevents androgen, estrogen, and glucocorticoid synthesis; causes mineralocorticoid excess[citation needed]
* Cytochrome P450 oxidoreductase deficiency: prevents production of numerous but not all sex steroids,[1] as well as other metabolic reactions

### Androgen- and estrogen-specific

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* 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[citation needed]
* 5α-Reductase 2 deficiency: prevents the conversion of testosterone to dihydrotestosterone; causes androgen deficiency in males[citation needed]
* Aromatase deficiency: prevents estrogen synthesis; causes androgen excess in females[citation needed]
* Aromatase excess: causes excessive conversion of androgens to estrogens; results in estrogen excess in both sexes and androgen deficiency in males.[citation needed]

### Glucocorticoid- and mineralocorticoid-specific

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

### Miscellaneous

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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]

## See also

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* Inborn error of metabolism
* Disorders of sex development
* Congenital adrenal hyperplasia
* Adrenal insufficiency
* Hypogonadism (hypoandrogenism and hypoestrogenism)
* Hypergonadism (hyperandrogenism and hyperestrogenism)
* Delayed puberty and precocious puberty
* Intersex
* Steroid hormone
* Corticosteroid (glucocorticoid, mineralocorticoid)
* Sex steroid (androgen, estrogen, and progestogen)
* Neuroactive steroid
* Hypothalamus and pituitary gland
* Adrenal cortex and gonad (testicle and ovary)
* HPA axis and HPG axis

## References

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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; Flück, Christa E; Audí, Laura; Pandey, Amit V (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. hdl:10668/15112. PMID 32060549.
2. ^ Fernández-Cancio, Mónica; Camats, Núria; Flück, Christa E.; Zalewski, Adam; Dick, Bernhard; Frey, Brigitte M.; Monné, Raquel; Torán, Núria; Audí, Laura (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". Pharmaceuticals. 11 (2): 37. doi:10.3390/ph11020037. PMC 6027421. PMID 29710837.
3. ^ Karges B, Karges W, de Roux N (2003). "Clinical and molecular genetics of the human GnRH receptor". Human Reproduction Update. 9 (6): 523–30\. doi:10.1093/humupd/dmg040. PMID 14714589.
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. Retrieved 11 June 2012.
5. ^ Mark A. Sperling (25 April 2008). Pediatric Endocrinology E-Book. Elsevier Health Sciences. p. 35\. ISBN 978-1-4377-1109-7. Retrieved 11 June 2012.

## Further reading

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* Miller WL, Auchus RJ (February 2011). "The molecular biology, biochemistry, and physiology of human steroidogenesis and its disorders". Endocrine Reviews. 32 (1): 81–151\. doi:10.1210/er.2010-0013. PMC 3365799. PMID 21051590. Archived from the original on April 14, 2013.

## External links

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Classification|

* MeSH: D043202

|

* v
* t
* e

Inborn errors of steroid metabolism

Mevalonate
pathway|

* HMG-CoA lyase deficiency

* Hyper-IgD syndrome
* Mevalonate kinase deficiency

To cholesterol|

* 7-Dehydrocholesterol path: Hydrops-ectopic calcification-moth-eaten skeletal dysplasia
* CHILD syndrome
* Conradi–Hünermann syndrome
* Lathosterolosis
* Smith–Lemli–Opitz syndrome

* desmosterol path: Desmosterolosis

Steroids|

| Corticosteroid
(including CAH)|

* aldosterone: Glucocorticoid remediable aldosteronism

* cortisol/cortisone: CAH 17α-hydroxylase
* CAH 11β-hydroxylase

* both: CAH 3β-dehydrogenase
* CAH 21-hydroxylase
* Apparent mineralocorticoid excess syndrome/11β-dehydrogenase

|

Sex steroid|

| To androgens|

* 17α-Hydroxylase deficiency
* 17,20-Lyase deficiency
* Cytochrome b5 deficiency
* 3β-Hydroxysteroid dehydrogenase deficiency
* 17β-Hydroxysteroid dehydrogenase deficiency
* 5α-reductase 2 deficiency
* Pseudovaginal perineoscrotal hypospadias

|

To estrogens|

* Aromatase deficiency
* Aromatase excess syndrome

Other|

* X-linked ichthyosis
* Antley–Bixler syndrome

* v
* t
* e

Adrenal gland disorder

Hyperfunction|

| Aldosterone|

* Hyperaldosteronism
* Primary aldosteronism
* Conn syndrome
* Bartter syndrome
* Glucocorticoid remediable aldosteronism
* AME
* Liddle's syndrome
* 17α CAH
* Pseudohypoaldosteronism

|

Cortisol|

* Cushing's syndrome
* Pseudo-Cushing's syndrome
* Steroid-induced osteoporosis

Sex hormones|

* 21α CAH
* 11β CAH

Hypofunction|

| Aldosterone|

* Hypoaldosteronism
* 21α CAH
* 11β CAH

|

Cortisol|

* CAH
* Lipoid
* 3β
* 11β
* 17α
* 21α

Sex hormones|

* 17α CAH
* Inborn errors of steroid metabolism

Adrenal insufficiency|

* Adrenal crisis
* Adrenalitis
* Xanthogranulomatous
* Addison's disease
* Waterhouse–Friderichsen syndrome

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