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Gitelman syndrome

 

Gitelman syndrome

Gitelman syndrome
Classification and external resources
ICD-10 N25.8 + E87.6 + E83.4
OMIM 263800
DiseasesDB 31860
eMedicine article/238670
MeSH D053579

Gitelman syndrome is an autosomal recessive kidney disorder characterized by hypokalemic metabolic alkalosis with hypocalciuria, and hypomagnesemia. It is caused by loss of function mutations of the thiazide sensitive sodium-chloride symporter (also known as NCC, NCCT, or TSC) located in the distal convoluted tubule.[1]

Gitelman syndrome was formerly considered a subset of Bartter syndrome until the distinct genetic and molecular bases of these disorders were identified. Bartter syndrome is also an autosomal recessive hypokalemic metabolic alkalosis, but it derives from a mutation to the NKCC2 found in the thick ascending limb of the loop of Henle.[2]

Contents

  • Cause 1
  • Presentation 2
  • Eponym 3
  • References 4
  • External links 5

Cause

A model of transport mechanisms in the distal convoluted tubule. Sodium-chloride (NaCl) enters the cell via the apical thiazide-sensitive NCC and leaves the cell through the basolateral Cl channel (ClC-Kb), and the Na+/K+-ATPase. Indicated also are the recently identified magnesium channel TRPM6 in the apical membrane, and a putative Na/Mg exchanger in the basolateral membrane. These transport mechanisms play a role in familial hypokalemia-hypomagnesemia or Gitelman's syndrome.
Gitelman syndrome has an autosomal recessive pattern of inheritance.

Gitelman's syndrome is linked to inactivating mutations in the SLC12A3 gene resulting in a loss of function of the encoded thiazide-sensitive sodium-chloride co-transporter (NCCT). This cell membrane protein participates in the control of ion homeostasis at the distal convoluted tubule portion of the nephron.

Gitelman's syndrome is an autosomal-recessive disorder: one defective allele has to be inherited from each parent.

Presentation

People suffering from Gitelman's syndrome present symptoms which are identical to those of patients who are on thiazide diuretics[3]

Clinical symptoms for this disease are hypochloremic metabolic alkalosis, hypokalemia, and hypocalciuria. Hypomagnesemia is present in many but not all cases. In contrast to patients with Gordon's syndrome, those suffering from Gitelman's syndrome are generally normotensive or hypotensive. Sufferers of Gitelman's syndrome-linked mutations are often complain of severe muscular cramps, numbness or weakness expressed as extreme fatigue or irritability. More severe symptoms such as tetany and paralysis have commonly been reported.Cardiac arrhythmia on ECG and sudden cardiac death and long QT have been reported due to low potassium levels. Phenotypic variations observed among patients probably result from differences in their genetic background and may depend on which particular amino acid in the NCCT protein has been mutated.

See Naesens et al. for a recent review.[4]

Eponym

It is named for Hillel J. Gitelman (1932–2015), an American physician.[5][6][7]

References

  1. ^ Simon DB, Nelson-Williams C, Bia MJ, Ellison D, Karet FE, Molina AM, Vaara I, Iwata F, Cushner HM, Koolen M, Gainza FJ, Gitleman HJ, Lifton RP (Jan 1996). "Gitelman's variant of Bartter's syndrome, inherited hypokalaemic alkalosis, is caused by mutations in the thiazide-sensitive Na-Cl cotransporter.". Nat. Genet. 12 (1): 24–30.  
  2. ^ Simon DB, Karet FE, Hamdan JM, DiPietro A, Sanjad SA, Lifton RP (June 1996). "Bartter's syndrome, hypokalaemic alkalosis with hypercalciuria, is caused by mutations in the Na-K-2Cl cotransporter NKCC2". Nat. Genet. 13 (2): 183–8.  
  3. ^ O'Shaughnessy KM, Karet FE (2004). "Salt handling and hypertension". J. Clin. Invest. 113 (8): 1075–81.  
  4. ^ Naesens M, Steels P, Verberckmoes R, Vanrenterghem Y, Kuypers D (2004). "Bartter's and Gitelman's syndromes: from gene to clinic". Nephron. Physiology 96 (3): p65–78.  
  5. ^ synd/2329 at Who Named It?
  6. ^ Gitelman HJ, Graham JB, Welt LG (1966). "A new familial disorder characterized by hypokalemia and hypomagnesemia". Trans. Assoc. Am. Physicians 79: 221–35.  
  7. ^ Unwin RJ, Capasso G (2006). "Bartter's and Gitelman's syndromes: their relationship to the actions of loop and thiazide diuretics" ( 

External links

  • Gitelman Syndrome Online Patient Resource
  • The Bartter Site
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