The SLC12A3 gene encodes the thiazide-sensitive sodium-chloride cotransporter (also known as NCC, NCCT, or TSC), which can be found in the distal convoluted tubule of the kidney.

The effect is an electrolyte imbalance similar to that seen with thiazide diuretic therapy (which causes pharmacological inhibition of NCC activity).

[2] Abnormal heart rhythms and a prolonged QT interval can be detected on electrocardiogram[2] and cases of sudden cardiac death have been reported due to low potassium levels.

Quality of life is decreased in Gitelman syndrome[7] 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.

[15] Furthermore, continued action of the basolateral Na+/K+-ATPase might create an electrical gradient favourable for the reabsorption of divalent cations by secondary active transport.

RAAS activation is a byproduct of the failure of the distal convoluted tubule in reabsorbing electrolytes, specifically sodium and chloride leading to cellular dehydration.

[16] The pathognomonic clinical markers include low serum levels of potassium, sodium, chloride, and magnesium in the blood as a result of urinary excretion.

The symptomatic features of this syndrome are highly variable ranging from asymptomatic to mild manifestations (weakness, cramps) to severe symptoms (tetany, paralysis, rhabdomyolysis).

Dietary modification of a high salt diet incorporated with[16] potassium and magnesium supplementation to normalize blood levels is the mainstay of treatment.

[2] Diarrhea is a common side effect of oral magnesium which can make replacement by mouth difficult but dividing the dose to 3-4 times a day is better tolerated.

Aldosterone antagonists (such as spironolactone or eplerenone) or epithelial sodium channel blockers such as amiloride have also been suggested as possible treatments, because they decrease urinary wasting of potassium.

However, a consensus expert statement from 2017 warns that such drugs should only be used with caution in Gitelman syndrome because of the possible side effects (e.g., aggravated sodium depletion).

[2] In patients with early onset of the disease such as infants and children, indomethacin is the drug of choice utilized to treat growth disturbances.

[16] Indomethacin in a study by Blanchard et al. 2015 was shown to increase serum potassium levels, and decrease renin concentration.

[16] Medications that extend or prolong the QT interval (macrolides, antihistamines, beta-2 agonists) should be avoided in these patients to prevent cardiac death.

[9] The condition is named for Hillel Jonathan Gitelman (1932– January 12, 2015), an American nephrologist working at University of North Carolina School of Medicine.