Pseudohypoaldosteronism

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Pseudohypoaldosteronism
Aldosterone-2D-skeletal.svg
In pseudohypoaldosteronism, aldosterone is elevated (hyperaldosteronism), but because the body fails to respond to it, it appears similar to hypoaldosteronism.
SpecialtyUrology Edit this on Wikidata

Pseudohypoaldosteronism (PHA) is a condition that mimics hypoaldosteronism.[1] However, the condition is due to a failure of response to aldosterone, and levels of aldosterone are actually elevated, due to a lack of feedback inhibition.

History[edit]

This syndrome was first described by Cheek and Perry in 1958.[2] Later pediatric endocrinologist Aaron Hanukoglu reported that there are two independent forms of PHA with different inheritance patterns: A renal form with autosomal dominant inheritance exhibiting salt loss mainly from the kidneys, and a multi-system form with autosomal recessive form exhibiting salt loss from kidney, lung, and sweat and salivary glands.[3] [4]

The hereditary lack of responsiveness to aldosterone could be due to at least two possibilities: 1. A mutation in the mineralocorticoid receptor that binds aldosterone, or 2. A mutation in a gene that is regulated by aldosterone. Linkage analysis on patients suffering from the severe form of PHA excluded the possibility of linkage of the disease with the mineralocorticoid receptor gene region. [5] Later, the severe form of PHA was discovered to be due to mutations in the genes SCNN1A, SCNN1B, and SCNN1G that code for the epithelial sodium channel subunits, α, β, and γ, respectively.[6]

A stop mutation in the SCNN1A gene has been shown to be associated with female infertility.[7]

Types[edit]

Type OMIM Gene Inheritance Description
PHA1A 177735 MLR Autosomal dominant with sodium wasting
PHA1B 264350 SCNN1A, SCNN1B, SCNN1G of the epithelial sodium channel Autosomal recessive with sodium wasting
PHA2 145260 WNK4, WNK1 without sodium wasting. TRPV6 may be involved.[8]

Treatment[edit]

Treatment of severe forms of PHA requires relatively large amounts of sodium chloride.[9] These conditions also involve hyperkalemia.[10]

See also[edit]

References[edit]

  1. ^ "Pseudohypoaldosteronism: Overview - eMedicine Pediatrics: General Medicine". Retrieved 2009-03-06.
  2. ^ CHEEK DB, PERRY JW (1958). "A salt wasting syndrome in infancy". Arch Dis Child. 33 (169): 252–6. PMC 2012226. PMID 13545877.
  3. ^ Hanukoglu A (Nov 1991). "Type I pseudohypoaldosteronism includes two clinically and genetically distinct entities with either renal or multiple target organ defects". The Journal of Clinical Endocrinology and Metabolism. 73 (5): 936–44. doi:10.1210/jcem-73-5-936. PMID 1939532.
  4. ^ Hanukoglu I, Hanukoglu A (Jan 2016). "Epithelial sodium channel (ENaC) family: Phylogeny, structure-function, tissue distribution, and associated inherited diseases". Gene. 579 (2): 95–132. doi:10.1016/j.gene.2015.12.061. PMC 4756657. PMID 26772908.
  5. ^ Chung E, Hanukoglu A, Rees M, Thompson R, Dillon M, Hanukoglu I, et al. (1995). "Exclusion of the locus for autosomal recessive pseudohypoaldosteronism type 1 from the mineralocorticoid receptor gene region on human chromosome 4q by linkage analysis". J Clin Endocrinol Metab. 80 (11): 3341–5. doi:10.1210/jcem.80.11.7593448. PMID 7593448.
  6. ^ Chang SS, Grunder S, Hanukoglu A, Rösler A, Mathew PM, Hanukoglu I, et al. (1996). "Mutations in subunits of the epithelial sodium channel cause salt wasting with hyperkalaemic acidosis, pseudohypoaldosteronism type 1". Nat Genet. 12 (3): 248–53. doi:10.1038/ng0396-248. PMID 8589714.
  7. ^ Boggula VR, Hanukoglu I, Sagiv R, Enuka Y, Hanukoglu A (October 2018). "Expression of the epithelial sodium channel (ENaC) in the endometrium - Implications for fertility in a patient with pseudohypoaldosteronism". The Journal of Steroid Biochemistry and Molecular Biology. 183: 137–141. doi:10.1016/j.jsbmb.2018.06.007. PMID 29885352.
  8. ^ Yang SS, Hsu YJ, Chiga M, Rai T, Sasaki S, Uchida S, Lin SH (Apr 2010). "Mechanisms for hypercalciuria in pseudohypoaldosteronism type II-causing WNK4 knock-in mice". Endocrinology. 151 (4): 1829–36. doi:10.1210/en.2009-0951. PMID 20181799.
  9. ^ Hanukoglu A, Hanukoglu I (2010). "Clinical improvement in patients with autosomal recessive pseudohypoaldosteronism and the necessity for salt supplementation". Clinical and Experimental Nephrology. 14 (5): 518–519. doi:10.1007/s10157-010-0326-8. PMID 20661616.
  10. ^ Pseudohypoaldosteronism at the US National Library of Medicine Medical Subject Headings (MeSH)

External links[edit]

Classification
External resources