AI Article Synopsis
- Apparent mineralocorticoid excess (AME) is a genetic condition that leads to low-renin hypertension, low aldosterone levels, and high cortisol to cortisone metabolite ratios due to mutations in the HSD11B2 gene.* -
- It affects the enzyme 11β-HSD2, which converts cortisol to cortisone, and has over 50 identified mutations that impair enzyme function through various molecular mechanisms.* -
- Early and accurate diagnosis through genetic testing is crucial for effective management of AME, helping to prevent severe health complications related to target organ damage.*
Article Abstract
Apparent mineralocorticoid excess is an autosomal recessive form of monogenic disease characterized by juvenile resistant low-renin hypertension, marked hypokalemic alkalosis, low aldosterone levels, and high ratios of cortisol to cortisone metabolites. It is caused by defects in the HSD11B2 gene, encoding the enzyme 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), which is primarily involved in the peripheral conversion of cortisol to cortisone. To date, over 50 deleterious HSD11B2 mutations have been identified worldwide. Multiple molecular mechanisms function in the lowering of 11β-HSD2 activity, including damaging protein stability, lowered affinity for the substrate and cofactor, and disrupting the dimer interface. Genetic polymorphism, environmental factors as well as epigenetic modifications may also offer an implicit explanation for the molecular pathogenesis of AME. A precise diagnosis depends on genetic testing, which allows for early and specific management to avoid the morbidity and mortality from target organ damage. In this review, we provide insights into the molecular genetics of classic and non-classic apparent mineralocorticoid excess and aim to offer a comprehensive overview of this monogenic disease.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9632093 | PMC |
| http://dx.doi.org/10.1186/s12967-022-03698-9 | DOI Listing |
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