An inborn error of steroid metabolism is an

inborn error of metabolism Inborn errors of metabolism form a large class of genetic diseases involving congenital disorders of enzyme activities. The majority are due to defects of single genes that code for enzymes that facilitate conversion of various substances (substrat ...

due to defects in steroid metabolism.

Types

A variety of conditions of abnormal

steroidogenesis A steroid is an organic compound with four fused rings (designated A, B, C, and D) arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes that alter memb ...

exist due to

genetic mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mitosis ...

s in the

steroidogenic enzyme __NOTOC__ Steroidogenic enzymes are enzymes that are involved in steroidogenesis and steroid biosynthesis. They are responsible for the biosynthesis of the steroid hormones, including sex steroids (androgens, estrogens, and progestogens) and co ...

s involved in the process, of which include:

Generalized

* 20,22-Desmolase (P450scc) deficiency: blocks production of all

steroid hormone A steroid hormone is a steroid that acts as a hormone. Steroid hormones can be grouped into two classes: corticosteroids (typically made in the adrenal cortex, hence ''cortico-'') and sex steroids (typically made in the gonads or placenta). Wit ...

s from

cholesterol Cholesterol is the principal sterol of all higher animals, distributed in body Tissue (biology), tissues, especially the brain and spinal cord, and in Animal fat, animal fats and oils. Cholesterol is biosynthesis, biosynthesized by all anima ...

* 3β-Hydroxysteroid dehydrogenase 2 deficiency: impairs

progestogen Progestogens, also sometimes written progestins, progestagens or gestagens, are a class of natural or synthetic steroid hormones that bind to and activate the progesterone receptors (PR). Progesterone is the major and most important progestoge ...

and

androgen An androgen (from Greek ''andr-'', the stem of the word meaning ) is any natural or synthetic steroid hormone that regulates the development and maintenance of male characteristics in vertebrates by binding to androgen receptors. This includes ...

metabolism; prevents the synthesis of

estrogen Estrogen (also spelled oestrogen in British English; see spelling differences) is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three ...

glucocorticoid Glucocorticoids (or, less commonly, glucocorticosteroids) are a class of corticosteroids, which are a class of steroid hormones. Glucocorticoids are corticosteroids that bind to the glucocorticoid receptor that is present in almost every vertebra ...

s, and

mineralocorticoid Mineralocorticoids are a class of corticosteroids, which in turn are a class of steroid hormones. Mineralocorticoids are produced in the adrenal cortex and influence salt and water balances (electrolyte balance and fluid balance). The primary ...

s; 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 steroid Sex hormones, also known as sex steroids, gonadocorticoids and gonadal steroids, are steroid hormones that interact with vertebrate steroid hormone receptors. The sex hormones include the androgens, estrogens, and progestogens. Their effects a ...

s, 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 Methemoglobin (British: methaemoglobin, shortened MetHb) (pronounced "met-hemoglobin") is a hemoglobin ''in the form of metalloprotein'', in which the iron in the heme group is in the Fe3+ (ferric) state, not the Fe2+ (ferrous) of normal hemoglobin ...

and/or

methemoglobinemia Methemoglobinemia, or methaemoglobinaemia, is a condition of elevated methemoglobin in the blood. Symptoms may include headache, dizziness, shortness of breath, nausea, poor muscle coordination, and blue-colored skin (cyanosis). Complications ma ...

* 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 5α-Reductase 2 deficiency (5αR2D) is an autosomal recessive condition caused by mutations impairing the function of ''SRD5A2'', a gene located on chromosome 2 and encoding the enzyme 5α-reductase type 2 (5αR2). 5αR2 is expressed in specific ...

: prevents the conversion of

testosterone Testosterone is the primary male sex hormone and androgen in Male, males. In humans, testosterone plays a key role in the development of Male reproductive system, male reproductive tissues such as testicles and prostate, as well as promoting se ...

dihydrotestosterone Dihydrotestosterone (DHT, 5α-dihydrotestosterone, 5α-DHT, androstanolone or stanolone) is an endogenous androgen sex steroid and hormone primarily involved in the growth and repair of the prostate and the penis, as well as the production o ...

; 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 ''

receptor Receptor may refer to: * Sensory receptor, in physiology, any neurite structure that, on receiving environmental stimuli, produces an informative nerve impulse *Receptor (biochemistry), in biochemistry, a protein molecule that receives and respond ...

s'', 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 No activating mutations of the GnRH receptor in humans have been described in the

medical literature Medical literature is the scientific literature of medicine: articles in journals and texts in books devoted to the field of medicine. Many references to the medical literature include the health care literature generally, including that of denti ...

, and only one of the FSH receptor has been described, which presented as asymptomatic.

References

External links

{{Adrenal gland disorder Adrenal gland disorders Cholesterol and steroid metabolism disorders Endocrine gonad disorders Genetic diseases and disorders Rare diseases