Gitelman Syndrome

Gitelman syndrome is an autosomal recessive tubulopathy caused by loss-of-function variants in SLC12A3 (thiazide-sensitive sodium chloride cotransporter, NCC) in the distal convoluted tubule.

• Prevalence 1 in 40,000; heterozygous carriers about 1% of Caucasians.
• Mimics chronic thiazide use: hypokalaemia, metabolic alkalosis, hypomagnesaemia, hypocalciuria, hyperreninaemic hyperaldosteronism with normal or low blood pressure.
• Usually diagnosed in adolescence or adulthood; milder than Bartter syndrome.
• Complications: chondrocalcinosis, prolonged QT with arrhythmia (hypokalaemia and hypomagnesaemia), fatigue, tetany, impaired quality of life, rarely CKD (mild).

• Fatigue, muscle weakness, cramps, tetany, paraesthesia, salt craving, polyuria, nocturia.
• Palpitations, QT prolongation, syncope; chondrocalcinosis with joint pain.
• Often asymptomatic and discovered incidentally by hypokalaemia.
• Normal growth in most, blood pressure low-normal.
• Pregnancy may worsen hypokalaemia.

• Hypokalaemia (2.0 to 3.0 mmol/L), hypomagnesaemia (under 0.7 mmol/L), metabolic alkalosis, hypocalciuria (urinary calcium/creatinine under 0.2 mmol/mmol), urinary potassium wasting, elevated renin/aldosterone.
• Urinary chloride high, fractional excretion of chloride over 0.5%.
• Genetic testing for SLC12A3 (biallelic variants); exclude CLCNKB (Bartter type III), HNF1B, EAST syndrome.
• Exclude surreptitious thiazide or laxative use or vomiting (urine diuretic screen, low urinary chloride in vomiting).
• Thiazide test (blunted response in Gitelman) is rarely done.
• ECG for QT interval; bone mineral density.

• Liberal salt intake and potassium-rich diet.
• Magnesium replacement first line, as it improves potassium retention: magnesium oxide 400 to 800 mg daily, magnesium sulfate or chloride slow-release 12 to 24 mmol/day in divided doses (diarrhoea limits dose; split into small doses with meals, or magnesium lactate/aspartate).
• Potassium chloride 40 to 200 mmol/day in divided doses with food (liquid or slow release); target potassium over 3.0 mmol/L (ideally 3.5).
• Potassium-sparing diuretics: spironolactone 25 to 100 mg daily, eplerenone, amiloride 5 to 20 mg daily, triamterene; cautious ACE inhibitor/ARB.
• NSAIDs (indomethacin 50 to 100 mg daily) in refractory cases with caution (kidney and gastric toxicity).
• Avoid QT-prolonging drugs, laxatives, diuretics, and licorice.
• Cramps and tetany: oral magnesium; IV magnesium sulfate 2 g in acute symptomatic tetany or arrhythmia, IV potassium for severe hypokalaemia with ECG changes.
• Pregnancy: increase supplements, monitor electrolytes; avoid ACE inhibitors and spironolactone (use amiloride cautiously).
• Monitor electrolytes every 3 to 6 months, ECG, renal function, bone health.
• Genetic counselling.