Inborn errors of steroid metabolism
An inborn error of steroid metabolism is an inborn error of metabolism due to defects in steroid metabolism.
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
- Congenital adrenal hyperplasia due to [3β-hydroxysteroid dehydrogenase deficiency|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, as well as other metabolic reactions
Androgen- and estrogen-specific
- Isolated 17,20-lyase deficiency: prevents androgen and estrogen synthesis.
- * 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:- 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