Overview
Definition
An autosomal recessive renal tubular disorder characterized by hypokalemic metabolic alkalosis, hypomagnesemia, and profound hypocalciuria, mimicking thiazide diuretic action.
Epidemiology
Prevalence ~1-10 in 40,000. Often presents in late childhood or adulthood.
Etiology & Risk Factors
- Inactivating mutations in the SLC12A3 gene encoding the thiazide-sensitive sodium-chloride cotransporter (NCCT) in the distal convoluted tubule
Clinical Symptoms
- Muscle weakness, cramps, and spasms
- Fatigue and lethargy
- Paresthesias
- Polydipsia and polyuria
Clinical Approach
Diagnosis
- Hypokalemia and hypomagnesemia
- Metabolic alkalosis
- Low urinary calcium excretion (distinguishes from Bartter)
- Elevated renin and aldosterone
Management
- High-dose oral magnesium and potassium supplementation
- Potassium-sparing diuretics (Amiloride, Spironolactone) or NSAIDs if refractory
Complications
- Cardiac arrhythmias
- Chondrocalcinosis
- Growth retardation in children (rare)