Inborn errors of steroid metabolism

Inborn error of steroid metabolism
Classification and external resources
MeSH	D043202

An inborn error of steroid metabolism is an inborn error of metabolism due to defects in steroid metabolism.

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

18,20-Desmolase (P450scc) deficiency: blocks production of all steroid hormones from cholesterol
3β-Hydroxysteroid dehydrogenase type 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
Isolated 17,20-lyase deficiency: prevents androgen and estrogen synthesis
21-Hydroxylase deficiency: prevents glucocorticoid and mineralocorticoid synthesis; causes androgen excess in females
11β-Hydroxylase type 1 deficiency: impairs glucocorticoid and mineralocorticoid metabolism; causes glucocorticoid deficiency and mineralocorticoid excess as well as androgen excess in females
11β-Hydroxylase type 2 deficiency: impairs corticosteroid metabolism; results in excessive mineralocorticoid activity
18-Hydroxylase deficiency: impairs mineralocorticoid metabolism; results in mineralocorticoid deficiency
18-Hydroxylase overactivity: impairs mineralocorticoid metabolism; results in mineralocorticoid excess
17β-Hydroxysteroid dehydrogenase deficiency: impairs androgen and estrogen metabolism; results in androgen deficiency in males and androgen excess and estrogen deficiency in females
5α-Reductase type 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

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

No activating mutations of the GnRH receptor in humans have been described in the medical literature,^[1] and only one of the FSH receptor has been described, which presented as asymptomatic.^[2]^[3]

References

↑ 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.
↑ 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.
↑ 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.

Index of inborn errors of metabolism

Description	Metabolism Enzymes and pathways: citric acid cycle enzymes pentose phosphate intermediates glycoproteins enzymes glycosaminoglycans proteoglycan enzymes phospholipid metabolism cholesterol and steroid intermediates sphingolipids enzymes eicosanoids enzymes amino acid intermediates urea cycle enzymes nucleotide intermediates

Disorders	Citric acid cycle and electron transport chain Glycoprotein Proteoglycan Fatty-acid Phospholipid Cholesterol and steroid Eicosanoid Amino acid Purine-pyrimidine Heme metabolism Symptoms and signs

Treatment	Drugs other

Index of hormones

Description	Glands Hormones thyroid intermediates metabolism mineralocorticoids Physiology Development

Disease	Diabetes Congenital Neoplasms and cancer Other Symptoms and signs eponymous

Treatment	Procedures Drugs calcium balance corticosteroids oral hypoglycemics pituitary and hypothalamic thyroid

Diseases of the endocrine system (E00–E35, 240–259)

Pancreas/
glucose
metabolism

Hypofunction	Diabetes mellitus types: type 1 type 2 MODY 1 2 3 4 5 6 complications coma angiopathy ketoacidosis nephropathy neuropathy retinopathy cardiomyopathy insulin receptor (Rabson–Mendenhall syndrome) Insulin resistance

Hyperfunction	Hypoglycemia beta cell (Hyperinsulinism) G cell (Zollinger–Ellison syndrome)

Hypothalamic/
pituitary axes

Hypothalamus

gonadotropin
- Kallmann syndrome
- Adiposogenital dystrophy
CRH (Tertiary adrenal insufficiency)
vasopressin (Neurogenic diabetes insipidus)
general (Hypothalamic hamartoma)

Pituitary

Hyperpituitarism	anterior Acromegaly Hyperprolactinaemia Pituitary ACTH hypersecretion posterior (SIADH) general (Nelson's syndrome)

Hypopituitarism	anterior Kallmann syndrome Growth hormone deficiency ACTH deficiency/Secondary adrenal insufficiency GnRH insensitivity FSH insensitivity LH/hCG insensitivity posterior (Neurogenic diabetes insipidus) general Empty sella syndrome Pituitary apoplexy Sheehan's syndrome Lymphocytic hypophysitis

Thyroid

Hypothyroidism	Iodine deficiency Cretinism Congenital hypothyroidism Myxedema Euthyroid sick syndrome

Hyperthyroidism	Hyperthyroxinemia Thyroid hormone resistance Familial dysalbuminemic hyperthyroxinemia Hashitoxicosis Thyrotoxicosis factitia Graves' disease

Thyroiditis	Acute infectious Subacute De Quervain's Subacute lymphocytic Autoimmune/chronic Hashimoto's Postpartum Riedel's

Goitre	Endemic goitre Toxic nodular goitre Toxic multinodular goiter Thyroid nodule

Parathyroid

Hypoparathyroidism	Hypoparathyroidism Pseudohypoparathyroidism Pseudopseudohypoparathyroidism

Hyperparathyroidism	Primary Secondary Tertiary Osteitis fibrosa cystica

Adrenal

Hyperfunction	aldosterone: Hyperaldosteronism/Primary aldosteronism Conn syndrome Bartter syndrome Glucocorticoid remediable aldosteronism AME Liddle's syndrome 17α CAH cortisol: Cushing's syndrome (Pseudo-Cushing's syndrome) sex hormones: 21α CAH 11β CAH

Hypofunction/ Adrenal insufficiency (Addison's, WF)	aldosterone: Hypoaldosteronism 21α CAH 11β CAH cortisol: CAH Lipoid 3β 11β 17α 21α sex hormones: 17α CAH

Gonads

testicular: enzymatic
- 5α-reductase deficiency
- 17β-hydroxysteroid dehydrogenase deficiency
- aromatase excess syndrome)
Androgen receptor (Androgen insensitivity syndrome)

general: Hypogonadism (Delayed puberty)
Hypergonadism
- Precocious puberty
Hypoandrogenism
Hypoestrogenism
Hyperandrogenism
Hyperestrogenism

Height

Multiple

Autoimmune polyendocrine syndrome multiple
- APS1
- APS2
Carcinoid syndrome
Multiple endocrine neoplasia
- 1
- 2A
- 2B
Progeria
Woodhouse-Sakati syndrome

Index of hormones

Description	Glands Hormones thyroid intermediates metabolism mineralocorticoids Physiology Development

Disease	Diabetes Congenital Neoplasms and cancer Other Symptoms and signs eponymous

Treatment	Procedures Drugs calcium balance corticosteroids oral hypoglycemics pituitary and hypothalamic thyroid

Inborn errors of steroid metabolism

See also

References

Further reading