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Apparent mineralocorticoid excess syndrome

January 01, 1970

Apparent mineralocorticoid excess is an autosomal recessive[2] disorder causing hypertension (high blood pressure), hypernatremia (increased blood sodium concentration) and hypokalemia (decreased blood potassium concentration). It results from mutations in the HSD11B2 gene, which encodes the kidney isozyme of 11β-hydroxysteroid dehydrogenase type 2. In an unaffected individual, this isozyme inactivates circulating cortisol to the less active metabolite cortisone. The inactivating mutation leads to elevated local concentrations of cortisol in the aldosterone sensitive tissues like the kidney. Cortisol at high concentrations can cross-react and activate the mineralocorticoid receptor due to the non-selectivity of the receptor, leading to aldosterone-like effects in the kidney. This is what causes the hypokalemia, hypertension, and hypernatremia associated with the syndrome. Patients often present with severe hypertension and end-organ changes associated with it like left ventricular hypertrophy, retinal, renal and neurological vascular changes along with growth retardation and failure to thrive. In serum both aldosterone and renin levels are low.[3]

Apparent mineralocorticoid excess syndrome
Other namesAME, 11-beta-hydroxysteroid dehydrogenase deficiency type 2, Ulick syndrome.
Apparent mineralocorticoid excess syndrome has an autosomal recessive pattern of inheritance
SpecialtyMedical genetics, endocrinology 
SymptomsHypertension, hypokalemia, metabolic alkalosis, and low plasma renin activity.[1]

Signs and symptoms edit

This disorder presents similarly to hyperaldosteronism, leading to feedback inhibition of aldosterone. Common symptoms include hypertension, hypokalemia, metabolic alkalosis, and low plasma renin activity.[1]

DOC excess syndrome is an excessive secretion of 21-hydroxyprogesterone also called 11-Deoxycorticosterone from adrenal glands and may cause mineralocorticoid hypertension.[4][5][6]

Genetics edit

AME is inherited in an autosomal recessive manner.[2] This means the defective gene responsible for the disorder is located on an autosome, and two copies of the defective gene (one inherited from each parent) are required in order to be born with the disorder. The parents of an individual with an autosomal recessive disorder both carry one copy of the defective gene, but usually do not experience any signs or symptoms of the disorder.[7]

Diagnosis edit

Other conditions such as Liddle's Syndrome can mimic the clinical features of AME, so diagnosis can be made by calculating the ratio of free urinary cortisol to free urinary cortisone. Since AME patients create less cortisone, the ratio will much be higher than non-affected patients.[8] Alternatively, one could differentiate between the two syndromes by administering a potassium-sparing diuretic. Patients with Liddle's syndrome will only respond to a diuretic that binds the ENaC channel, whereas those with AME will respond to a diuretic that binds to ENaC or the mineralcorticoid receptor.[9]

Treatment edit

The treatment for AME is based on the blood pressure control with Aldosterone antagonist like Spironolactone which also reverses the hypokalemic metabolic alkalosis and other anti-hypertensives. Renal transplant is found curative in almost all clinical cases.[10] AME is exceedingly rare, with fewer than 100 cases recorded worldwide.[8]

History edit

Apparent mineralocorticoid excess is a rare form of monogenic hypertension that is transmitted as an autosomal recessive trait. The clinical symptoms of AME were first reported in 1974 by a Professor from Switzerland; Edmond A Werder in a 3-year-old girl with low birth weight, delayed growth, polydipsia, polyuria, and hypertension. In 1977, the US Professor Maria New identified patients with similar symptoms, characterized their biochemical profiles, and named the disease AME. Initially, it was speculated that HSD11B1 (encoding 11β-hydroxysteroid dehydrogenase type 1 [11β-HSD1]) was the causative gene but no mutation was detected in AME patients; thus, the focus was shifted to other candidate genes. In 1995, the US Professor Robert Wilson identified the first HSD11B2 mutation in several siblings with typical characteristics of AME from a consanguineous Iranian family, unraveling the genetic defects of AME. The molecular pathogenesis of AME primarily results from a deficiency in the enzyme 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), which is involved in the peripheral metabolism of cortisol. In 1999, B. Scott Nunez; another US professor, summarized the AME genotype–phenotype correlation by studying 14 affected children and proposed that clinical and/or biochemical parameters and enzyme activity were closely related [11]

Liquorice effect edit

Liquorice consumption may also cause a temporary form of AME due to its ability to block 11β-hydroxysteroid dehydrogenase type 2, in turn causing increased levels of cortisol.[12][13] Cessation of licorice consumption will reverse this form of AME.[14]

See also edit

References edit

  1. ^ a b Palermo, Mario; Quinkler, Marcus; Stewart, Paul M. (2004). "Apparent mineralocorticoid excess syndrome: an overview". Arquivos Brasileiros de Endocrinologia & Metabologia. 48 (5). FapUNIFESP (SciELO): 687–696. doi:10.1590/s0004-27302004000500015. ISSN 0004-2730. PMID 15761540.
  2. ^ a b Levtchenko, E. N.; Deinum, J.; Knoers, N. V. a. M.; Hermus, A. R.; Monnens, L. a. H.; Lenders, J. W. M. (2007). "Van gen naar ziekte; 'apparent mineralocorticoid excess'-syndroom, een syndroom met ogenschijnlijke overmaat aan mineralocorticoïden" [From gene to disease; 'apparent mineralocorticoid excess' syndrome, a syndrome with an apparent excess of mineral corticoids]. Nederlands Tijdschrift voor Geneeskunde (in Dutch). 151 (12): 692–694. hdl:11370/df94307a-2281-4450-93bf-a30c7bc2d0ab. PMID 17447595.
  3. ^ Al-Harbi, Taiba; Al-Shaikh, Adnan (1 January 2012). "Apparent mineralocorticoid excess syndrome: report of one family with three affected children". Journal of Pediatric Endocrinology and Metabolism. 25 (11–12): 1083–8. doi:10.1515/jpem-2012-0113. PMID 23329753. S2CID 21281031.
  4. ^ Marques, Pedro; Tufton, Nicola; Bhattacharya, Satya; Caulfield, Mark; Akker, Scott A (3 May 2019). "Hypertension due to a deoxycorticosterone-secreting adrenal tumour diagnosed during pregnancy". Endocrinology, Diabetes & Metabolism Case Reports. 2019. doi:10.1530/EDM-18-0164. PMC 6499913. PMID 31051469.
  5. ^ Gupta, Saurabh; Melendez, Jose; Khanna, Apurv (2010). "Deoxycorticosterone Producing Tumor as a Cause of Resistant Hypertension". Case Reports in Medicine. 2010: 372719. doi:10.1155/2010/372719. PMC 2909735. PMID 20671982.
  6. ^ Deoxycorticosterone (DOC) at eMedicine
  7. ^ "Autosomal recessive: MedlinePlus Medical Encyclopedia". MedlinePlus. Retrieved November 10, 2023.
  8. ^ a b Palermo M, Quinkler M, Stewart PM (Oct 2004). "Apparent mineralocorticoid excess syndrome: an overview" (PDF). Arq Bras Endocrinol Metabol. 48 (5): 687–696. doi:10.1590/S0004-27302004000500015. PMID 15761540.
  9. ^ DG, Warnock (2001). "Liddle's syndrome: genetics and mechanisms of Na+ channel defects". Contributions to Nephrology (136). Contrib Nephrol: 1–10. ISSN 0302-5144. PMID 11688373. Retrieved November 10, 2023.
  10. ^ Marshall, Ian; New, Maria I. (2003). "Mineralocorticoid Disorders, Genetic Basis of". Encyclopedia of Hormones. Elsevier. pp. 679–685. doi:10.1016/b0-12-341103-3/00105-4. ISBN 9780123411037.
  11. ^ Zhang, Lu, Yt. (2022). "Apparent mineralocorticoid excess: comprehensive overview of molecular genetics". Translational Medicine 2022. 20 (1): 500. doi:10.1186/s12967-022-03698-9. PMC 9632093. PMID 36329487.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  12. ^ "HSD11B2 Gene". GeneCards.
  13. ^ Sontia, Bruno; Mooney, Jan; Gaudet, Lise; Touyz, Rhian M. (February 2008). "Pseudohyperaldosteronism, Liquorice, and Hypertension". The Journal of Clinical Hypertension. 10 (2): 153–157. doi:10.1111/j.1751-7176.2008.07470.x. PMC 8109973. PMID 18256580. S2CID 20098685.
  14. ^ Gallacher, Stuart Declan; Tsokolas, Georgios; Dimitropoulos, Ioannis (2017). "Liquorice-induced apparent mineralocorticoid excess presenting in the emergency department". Clinical Medicine. 17 (1). Royal College of Physicians: 43–45. doi:10.7861/clinmedicine.17-1-43. ISSN 1470-2118. PMC 6297599. PMID 28148579.

External links edit

January 01, 1970
apparent, mineralocorticoid, excess, syndrome, apparent, mineralocorticoid, excess, autosomal, recessive, disorder, causing, hypertension, high, blood, pressure, hypernatremia, increased, blood, sodium, concentration, hypokalemia, decreased, blood, potassium, . Apparent mineralocorticoid excess is an autosomal recessive 2 disorder causing hypertension high blood pressure hypernatremia increased blood sodium concentration and hypokalemia decreased blood potassium concentration It results from mutations in the HSD11B2 gene which encodes the kidney isozyme of 11b hydroxysteroid dehydrogenase type 2 In an unaffected individual this isozyme inactivates circulating cortisol to the less active metabolite cortisone The inactivating mutation leads to elevated local concentrations of cortisol in the aldosterone sensitive tissues like the kidney Cortisol at high concentrations can cross react and activate the mineralocorticoid receptor due to the non selectivity of the receptor leading to aldosterone like effects in the kidney This is what causes the hypokalemia hypertension and hypernatremia associated with the syndrome Patients often present with severe hypertension and end organ changes associated with it like left ventricular hypertrophy retinal renal and neurological vascular changes along with growth retardation and failure to thrive In serum both aldosterone and renin levels are low 3 Apparent mineralocorticoid excess syndromeOther namesAME 11 beta hydroxysteroid dehydrogenase deficiency type 2 Ulick syndrome Apparent mineralocorticoid excess syndrome has an autosomal recessive pattern of inheritanceSpecialtyMedical genetics endocrinology SymptomsHypertension hypokalemia metabolic alkalosis and low plasma renin activity 1 Contents 1 Signs and symptoms 2 Genetics 3 Diagnosis 4 Treatment 5 History 6 Liquorice effect 7 See also 8 References 9 External linksSigns and symptoms editThis disorder presents similarly to hyperaldosteronism leading to feedback inhibition of aldosterone Common symptoms include hypertension hypokalemia metabolic alkalosis and low plasma renin activity 1 DOC excess syndrome is an excessive secretion of 21 hydroxyprogesterone also called 11 Deoxycorticosterone from adrenal glands and may cause mineralocorticoid hypertension 4 5 6 Genetics editAME is inherited in an autosomal recessive manner 2 This means the defective gene responsible for the disorder is located on an autosome and two copies of the defective gene one inherited from each parent are required in order to be born with the disorder The parents of an individual with an autosomal recessive disorder both carry one copy of the defective gene but usually do not experience any signs or symptoms of the disorder 7 Diagnosis editOther conditions such as Liddle s Syndrome can mimic the clinical features of AME so diagnosis can be made by calculating the ratio of free urinary cortisol to free urinary cortisone Since AME patients create less cortisone the ratio will much be higher than non affected patients 8 Alternatively one could differentiate between the two syndromes by administering a potassium sparing diuretic Patients with Liddle s syndrome will only respond to a diuretic that binds the ENaC channel whereas those with AME will respond to a diuretic that binds to ENaC or the mineralcorticoid receptor 9 Treatment editThe treatment for AME is based on the blood pressure control with Aldosterone antagonist like Spironolactone which also reverses the hypokalemic metabolic alkalosis and other anti hypertensives Renal transplant is found curative in almost all clinical cases 10 AME is exceedingly rare with fewer than 100 cases recorded worldwide 8 History editApparent mineralocorticoid excess is a rare form of monogenic hypertension that is transmitted as an autosomal recessive trait The clinical symptoms of AME were first reported in 1974 by a Professor from Switzerland Edmond A Werder in a 3 year old girl with low birth weight delayed growth polydipsia polyuria and hypertension In 1977 the US Professor Maria New identified patients with similar symptoms characterized their biochemical profiles and named the disease AME Initially it was speculated that HSD11B1 encoding 11b hydroxysteroid dehydrogenase type 1 11b HSD1 was the causative gene but no mutation was detected in AME patients thus the focus was shifted to other candidate genes In 1995 the US Professor Robert Wilson identified the first HSD11B2 mutation in several siblings with typical characteristics of AME from a consanguineous Iranian family unraveling the genetic defects of AME The molecular pathogenesis of AME primarily results from a deficiency in the enzyme 11b hydroxysteroid dehydrogenase type 2 11b HSD2 which is involved in the peripheral metabolism of cortisol In 1999 B Scott Nunez another US professor summarized the AME genotype phenotype correlation by studying 14 affected children and proposed that clinical and or biochemical parameters and enzyme activity were closely related 11 Liquorice effect editLiquorice consumption may also cause a temporary form of AME due to its ability to block 11b hydroxysteroid dehydrogenase type 2 in turn causing increased levels of cortisol 12 13 Cessation of licorice consumption will reverse this form of AME 14 See also editInborn errors of steroid metabolism 11b Hydroxylase I deficiency Hyperaldosteronism Pseudohyperaldosteronism Glucocorticoid remediable aldosteronism Aldosterone and aldosterone synthase Maria NewReferences edit a b Palermo Mario Quinkler Marcus Stewart Paul M 2004 Apparent mineralocorticoid excess syndrome an overview Arquivos Brasileiros de Endocrinologia amp Metabologia 48 5 FapUNIFESP SciELO 687 696 doi 10 1590 s0004 27302004000500015 ISSN 0004 2730 PMID 15761540 a b Levtchenko E N Deinum J Knoers N V a M Hermus A R Monnens L a H Lenders J W M 2007 Van gen naar ziekte apparent mineralocorticoid excess syndroom een syndroom met ogenschijnlijke overmaat aan mineralocorticoiden From gene to disease apparent mineralocorticoid excess syndrome a syndrome with an apparent excess of mineral corticoids Nederlands Tijdschrift voor Geneeskunde in Dutch 151 12 692 694 hdl 11370 df94307a 2281 4450 93bf a30c7bc2d0ab PMID 17447595 Al Harbi Taiba Al Shaikh Adnan 1 January 2012 Apparent mineralocorticoid excess syndrome report of one family with three affected children Journal of Pediatric Endocrinology and Metabolism 25 11 12 1083 8 doi 10 1515 jpem 2012 0113 PMID 23329753 S2CID 21281031 Marques Pedro Tufton Nicola Bhattacharya Satya Caulfield Mark Akker Scott A 3 May 2019 Hypertension due to a deoxycorticosterone secreting adrenal tumour diagnosed during pregnancy Endocrinology Diabetes amp Metabolism Case Reports 2019 doi 10 1530 EDM 18 0164 PMC 6499913 PMID 31051469 Gupta Saurabh Melendez Jose Khanna Apurv 2010 Deoxycorticosterone Producing Tumor as a Cause of Resistant Hypertension Case Reports in Medicine 2010 372719 doi 10 1155 2010 372719 PMC 2909735 PMID 20671982 Deoxycorticosterone DOC at eMedicine Autosomal recessive MedlinePlus Medical Encyclopedia MedlinePlus Retrieved November 10 2023 a b Palermo M Quinkler M Stewart PM Oct 2004 Apparent mineralocorticoid excess syndrome an overview PDF Arq Bras Endocrinol Metabol 48 5 687 696 doi 10 1590 S0004 27302004000500015 PMID 15761540 DG Warnock 2001 Liddle s syndrome genetics and mechanisms of Na channel defects Contributions to Nephrology 136 Contrib Nephrol 1 10 ISSN 0302 5144 PMID 11688373 Retrieved November 10 2023 Marshall Ian New Maria I 2003 Mineralocorticoid Disorders Genetic Basis of Encyclopedia of Hormones Elsevier pp 679 685 doi 10 1016 b0 12 341103 3 00105 4 ISBN 9780123411037 Zhang Lu Yt 2022 Apparent mineralocorticoid excess comprehensive overview of molecular genetics Translational Medicine 2022 20 1 500 doi 10 1186 s12967 022 03698 9 PMC 9632093 PMID 36329487 a href Template Cite journal html title Template Cite journal cite journal a CS1 maint multiple names authors list link HSD11B2 Gene GeneCards Sontia Bruno Mooney Jan Gaudet Lise Touyz Rhian M February 2008 Pseudohyperaldosteronism Liquorice and Hypertension The Journal of Clinical Hypertension 10 2 153 157 doi 10 1111 j 1751 7176 2008 07470 x PMC 8109973 PMID 18256580 S2CID 20098685 Gallacher Stuart Declan Tsokolas Georgios Dimitropoulos Ioannis 2017 Liquorice induced apparent mineralocorticoid excess presenting in the emergency department Clinical Medicine 17 1 Royal College of Physicians 43 45 doi 10 7861 clinmedicine 17 1 43 ISSN 1470 2118 PMC 6297599 PMID 28148579 External links editApparent mineralocorticoid excess at NIH s Office of Rare Diseases Retrieved from https en wikipedia org w index php title Apparent mineralocorticoid excess syndrome amp oldid 1212762118, wikipedia, wiki, book, books, library,

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