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| {{Infobox medical condition (new) | | {{Short description|Group of genetic disorders affecting steroid metabolism}} |
| | name = Inborn error of steroid metabolism | | {{Medical resources}} |
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| An '''inborn error of steroid metabolism''' is an [[inborn error of metabolism]] due to defects in [[steroid metabolism]].
| | '''Inborn errors of steroid metabolism''' are a group of [[genetic disorders]] that affect the [[biosynthesis]] and [[metabolism]] of [[steroids]]. These disorders result from mutations in the genes encoding enzymes involved in the steroidogenic pathway, leading to an accumulation or deficiency of specific steroid hormones. This can cause a variety of clinical manifestations depending on the specific enzyme affected and the role of the steroid hormones involved. |
| ==Types==
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| A variety of [[medical condition|condition]]s of abnormal [[steroidogenesis]] exist due to [[genetic mutation]]s in the [[steroidogenic enzyme]]s involved in the process, of which include:
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| ===Generalized=== | | ==Overview== |
| * [[Lipoid congenital adrenal hyperplasia|20,22-Desmolase (P450scc) deficiency]]: blocks production of all [[steroid hormone]]s from [[cholesterol]]
| | Steroid hormones are crucial for a wide range of physiological processes, including [[growth]], [[immune function]], [[metabolism]], and [[reproduction]]. They are synthesized from [[cholesterol]] through a series of enzymatic reactions occurring primarily in the [[adrenal glands]], [[gonads]], and [[placenta]]. Inborn errors of steroid metabolism can disrupt these pathways, leading to hormonal imbalances and clinical syndromes. |
| * [[Congenital adrenal hyperplasia due to 3β-hydroxysteroid dehydrogenase deficiency|3β-Hydroxysteroid dehydrogenase 2 deficiency]]: impairs [[progestogen]] and [[androgen]] metabolism; prevents the synthesis of [[estrogen]]s, [[glucocorticoid]]s, and [[mineralocorticoid]]s; causes androgen deficiency in males and androgen excess in females
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| * [[Congenital adrenal hyperplasia due to 17α-hydroxylase deficiency|Combined 17α-hydroxylase/17,20-lyase deficiency]]: impairs progestogen metabolism; prevents androgen, estrogen, and glucocorticoid synthesis; causes mineralocorticoid excess
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| * [[Cytochrome P450 oxidoreductase deficiency]]: prevents production of numerous but not all [[sex steroid]]s, as well as other [[metabolic reaction]]s
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| ===Androgen- and estrogen-specific=== | | ==Pathophysiology== |
| * [[Isolated 17,20-lyase deficiency]]: prevents androgen and estrogen synthesis
| | The steroidogenic pathway involves multiple steps, each catalyzed by a specific enzyme. Mutations in the genes encoding these enzymes can lead to: |
| ** [[Cytochrome b5 deficiency|Cytochrome b<sub>5</sub> deficiency]]: subtype of isolated 17,20-lyase deficiency; additionally results in elevated [[methemoglobin]] and/or [[methemoglobinemia]]
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| * [[17β-Hydroxysteroid dehydrogenase 3 deficiency]]: impairs androgen and estrogen metabolism; results in androgen deficiency in males and androgen excess and estrogen deficiency in females
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| * [[5α-Reductase 2 deficiency]]: prevents the conversion of [[testosterone]] to [[dihydrotestosterone]]; causes androgen deficiency in males
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| * [[Aromatase deficiency]]: prevents estrogen synthesis; causes androgen excess in females
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| * [[Aromatase excess syndrome|Aromatase excess]]: causes excessive conversion of androgens to estrogens; results in estrogen excess in both sexes and androgen deficiency in males
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| ===Glucocorticoid- and mineralocorticoid-specific===
| | * '''Enzyme deficiencies''': Resulting in reduced production of downstream steroid hormones. |
| * [[Congenital adrenal hyperplasia due to 21-hydroxylase deficiency|21-Hydroxylase deficiency]]: prevents glucocorticoid and mineralocorticoid synthesis; causes androgen excess in females | | * '''Substrate accumulation''': Leading to excess production of upstream precursors, which may be converted into alternative steroid products. |
| * [[Congenital adrenal hyperplasia due to 11β-hydroxylase deficiency|11β-Hydroxylase 1 deficiency]]: impairs glucocorticoid and mineralocorticoid metabolism; causes glucocorticoid deficiency and mineralocorticoid excess as well as androgen excess in females | |
| * [[Apparent mineralocorticoid excess syndrome|11β-Hydroxylase 2 deficiency]]: impairs corticosteroid metabolism; results in excessive mineralocorticoid activity
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| * [[18-Hydroxylase deficiency]]: prevents mineralocorticoid synthesis; results in mineralocorticoid deficiency
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| * [[Glucocorticoid remediable aldosteronism|18-Hydroxylase overactivity]]: impairs mineralocorticoid metabolism; results in mineralocorticoid excess
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| ===Miscellaneous===
| | The clinical consequences depend on the specific enzyme affected and the resulting hormonal imbalance. Commonly affected pathways include the synthesis of [[glucocorticoids]], [[mineralocorticoids]], and [[sex steroids]]. |
| In addition, several conditions of abnormal steroidogenesis due to genetic mutations in ''[[receptor (biochemistry)|receptor]]s'', as opposed to enzymes, also exist, including:
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| * [[Gonadotropin-releasing hormone insensitivity|Gonadotropin-releasing hormone (GnRH) insensitivity]]: prevents synthesis of sex steroids by the gonads in both sexes
| | ==Common Disorders== |
| * [[Follicle-stimulating hormone insensitivity|Follicle-stimulating (FSH) hormone insensitivity]]: prevents synthesis of sex steroids by the gonads in females; merely causes problems with fertility in males
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| * [[Leydig cell hypoplasia|Luteinizing hormone (LH) insensitivity]]: prevents synthesis of sex steroids by the gonads in males; merely causes problems with fertility in females
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| * [[Familial male-limited precocious puberty|Luteinizing hormone (LH) oversensitivity]]: causes androgen excess in males, resulting in precocious puberty; females are asymptomatic
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| No activating mutations of the GnRH receptor in humans have been described in the [[medical literature]],<ref name="pmid14714589">{{cite journal |vauthors=Karges B, Karges W, de Roux N | title = Clinical and molecular genetics of the human GnRH receptor | journal = Human Reproduction Update | volume = 9 | issue = 6 | pages = 523–30 | year = 2003 | pmid = 14714589 | doi = 10.1093/humupd/dmg040| url = http://humupd.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=14714589}}</ref> and only one of the FSH receptor has been described, which presented as asymptomatic.<ref name="NieschlagBehre2009">{{cite book | author1 = Eberhard Nieschlag | author2 = Hermann M. Behre | author3 = Susan Nieschlag | title = Andrology: Male Reproductive Health and Dysfunction | url = https://books.google.com/books?id=mEgckDNkonUC&pg=PA226 | accessdate = 11 June 2012 | date = 3 December 2009 | publisher = Springer | isbn = 978-3-540-78354-1 | page = 226}}</ref><ref name="Sperling2008">{{cite book | author = Mark A. Sperling | title = Pediatric Endocrinology E-Book | url = https://books.google.com/books?id=WIus0AIUhWIC&pg=PA35 | accessdate = 11 June 2012 | date = 25 April 2008 | publisher = Elsevier Health Sciences | isbn = 978-1-4377-1109-7 | page = 35}}</ref>
| | ===Congenital Adrenal Hyperplasia (CAH)=== |
| | [[Congenital adrenal hyperplasia]] is a group of disorders caused by enzyme deficiencies in the adrenal steroidogenic pathway. The most common form is 21-hydroxylase deficiency, leading to impaired synthesis of cortisol and aldosterone, with excess androgen production. |
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| ==See also== | | ===11β-Hydroxylase Deficiency=== |
| {{columns-list|colwidth=30em|
| | This condition results in impaired conversion of 11-deoxycortisol to cortisol, causing hypertension and virilization due to excess deoxycorticosterone and androgens. |
| * [[Inborn error of metabolism]]
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| * [[Disorders of sex development]]
| | ===17α-Hydroxylase Deficiency=== |
| * [[Congenital adrenal hyperplasia]]
| | A rare disorder characterized by hypertension and hypokalemia due to excess mineralocorticoids, with sexual infantilism due to deficient sex steroid production. |
| * [[Adrenal insufficiency]]
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| * [[Hypogonadism]] ([[hypoandrogenism]] and [[hypoestrogenism]])
| | ===3β-Hydroxysteroid Dehydrogenase Deficiency=== |
| * [[Hypergonadism]] ([[hyperandrogenism]] and [[hyperestrogenism]])
| | This disorder affects the conversion of pregnenolone to progesterone, leading to deficiencies in all steroid classes and ambiguous genitalia in genetic males. |
| * [[Delayed puberty]] and [[precocious puberty]]
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| * [[Intersex]]
| | ==Diagnosis== |
| * [[Steroid hormone]]
| | Diagnosis of inborn errors of steroid metabolism typically involves: |
| * [[Corticosteroid]] ([[glucocorticoid]], [[mineralocorticoid]]) | | |
| * [[Sex steroid]] ([[androgen]], [[estrogen]], and [[progestogen]]) | | * '''Clinical evaluation''': Assessment of symptoms and family history. |
| * [[Neuroactive steroid]] | | * '''Biochemical testing''': Measurement of hormone levels in blood and urine. |
| * [[Hypothalamus]] and [[pituitary gland]]
| | * '''Genetic testing''': Identification of mutations in genes encoding steroidogenic enzymes. |
| * [[Adrenal cortex]] and [[gonad]] ([[testicle]] and [[ovary]])
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| * [[Hypothalamic-pituitary-adrenal axis|HPA axis]] and [[hypothalamic-pituitary-gonadal axis|HPG axis]]
| | ==Management== |
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| | Management strategies depend on the specific disorder and may include: |
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| ==References==
| | * '''Hormone replacement therapy''': To correct deficiencies in cortisol, aldosterone, or sex steroids. |
| {{Reflist}}
| | * '''Surgical intervention''': For ambiguous genitalia or other anatomical abnormalities. |
| | * '''Monitoring and supportive care''': To manage complications such as hypertension or electrolyte imbalances. |
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| ==Further reading== | | ==Related pages== |
| * {{cite journal |vauthors=Miller WL, Auchus RJ | title = The molecular biology, biochemistry, and physiology of human steroidogenesis and its disorders | journal = Endocrine Reviews | volume = 32 | issue = 1 | pages = 81–151 |date=February 2011 | pmid = 21051590 | pmc = 3365799 | doi = 10.1210/er.2010-0013 | url = http://edrv.endojournals.org/cgi/pmidlookup?view=long&pmid=21051590}} | | * [[Steroid hormone]] |
| == External links ==
| | * [[Adrenal gland]] |
| {{Medical resources
| | * [[Endocrinology]] |
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| | * [[Genetic disorder]] |
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| {{Defects of cholesterol and steroid metabolism}}
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| {{Endocrine pathology}}
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| [[Category:Adrenal gland disorders]] | | [[Category:Genetic disorders]] |
| [[Category:Cholesterol and steroid metabolism disorders]] | | [[Category:Endocrinology]] |
| [[Category:Endocrine gonad disorders]] | | [[Category:Metabolic disorders]] |
| [[Category:Genetic diseases and disorders]]
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| [[Category:Rare diseases]]
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| [[Category:Intersex and medicine]]
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| {{dictionary-stub1}}
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| <gallery>
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| File:Steroidogenesis.svg
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| </gallery>
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Group of genetic disorders affecting steroid metabolism
Inborn errors of steroid metabolism are a group of genetic disorders that affect the biosynthesis and metabolism of steroids. These disorders result from mutations in the genes encoding enzymes involved in the steroidogenic pathway, leading to an accumulation or deficiency of specific steroid hormones. This can cause a variety of clinical manifestations depending on the specific enzyme affected and the role of the steroid hormones involved.
Overview
Steroid hormones are crucial for a wide range of physiological processes, including growth, immune function, metabolism, and reproduction. They are synthesized from cholesterol through a series of enzymatic reactions occurring primarily in the adrenal glands, gonads, and placenta. Inborn errors of steroid metabolism can disrupt these pathways, leading to hormonal imbalances and clinical syndromes.
Pathophysiology
The steroidogenic pathway involves multiple steps, each catalyzed by a specific enzyme. Mutations in the genes encoding these enzymes can lead to:
- Enzyme deficiencies: Resulting in reduced production of downstream steroid hormones.
- Substrate accumulation: Leading to excess production of upstream precursors, which may be converted into alternative steroid products.
The clinical consequences depend on the specific enzyme affected and the resulting hormonal imbalance. Commonly affected pathways include the synthesis of glucocorticoids, mineralocorticoids, and sex steroids.
Common Disorders
Congenital Adrenal Hyperplasia (CAH)
Congenital adrenal hyperplasia is a group of disorders caused by enzyme deficiencies in the adrenal steroidogenic pathway. The most common form is 21-hydroxylase deficiency, leading to impaired synthesis of cortisol and aldosterone, with excess androgen production.
11β-Hydroxylase Deficiency
This condition results in impaired conversion of 11-deoxycortisol to cortisol, causing hypertension and virilization due to excess deoxycorticosterone and androgens.
17α-Hydroxylase Deficiency
A rare disorder characterized by hypertension and hypokalemia due to excess mineralocorticoids, with sexual infantilism due to deficient sex steroid production.
3β-Hydroxysteroid Dehydrogenase Deficiency
This disorder affects the conversion of pregnenolone to progesterone, leading to deficiencies in all steroid classes and ambiguous genitalia in genetic males.
Diagnosis
Diagnosis of inborn errors of steroid metabolism typically involves:
- Clinical evaluation: Assessment of symptoms and family history.
- Biochemical testing: Measurement of hormone levels in blood and urine.
- Genetic testing: Identification of mutations in genes encoding steroidogenic enzymes.
Management
Management strategies depend on the specific disorder and may include:
- Hormone replacement therapy: To correct deficiencies in cortisol, aldosterone, or sex steroids.
- Surgical intervention: For ambiguous genitalia or other anatomical abnormalities.
- Monitoring and supportive care: To manage complications such as hypertension or electrolyte imbalances.
Related pages
