Bartter syndrome

Bartter syndrome is a group of rare inherited renal tubular disorders characterized by impaired salt reabsorption in the thick ascending limb of the loop of Henle in the kidneys. This leads to a distinctive set of metabolic abnormalities including hypokalemia (low potassium), hypochloremic metabolic alkalosis (elevated blood pH with low chloride), hyperreninemia, and hyperaldosteronism with normal to low blood pressure. The condition primarily affects the kidneys but has widespread consequences for the cardiovascular, muscular, and skeletal systems. Several subtypes of Bartter syndrome have been identified (types I through V), each caused by mutations in different genes involved in ion transport in the kidney. Type I is caused by mutations in SLC12A1 (encoding the NKCC2 cotransporter), type II by KCNJ1 (ROMK potassium channel), type III by CLCNKB (chloride channel Kb), type IVa by BSND (barttin), type IVb by combined CLCNKA and CLCNKB mutations, and type V by MAGED2 mutations. The antenatal/neonatal forms (types I, II, IV, and V) typically present with polyhydramnios, premature birth, life-threatening salt and water loss, polyuria, and failure to thrive. Type III, also known as classic Bartter syndrome, generally presents in infancy or early childhood with less severe symptoms including growth retardation, muscle weakness, cramps, fatigue, and salt craving. Some subtypes, particularly type IV, may also be associated with sensorineural deafness. Treatment is supportive and aimed at correcting electrolyte imbalances and minimizing complications. This typically includes potassium and magnesium supplementation, nonsteroidal anti-inflammatory drugs (NSAIDs) such as indomethacin to reduce renal prostaglandin production and improve electrolyte reabsorption, and potassium-sparing diuretics such as spironolactone or amiloride. ACE inhibitors may also be used in some cases. With appropriate lifelong management, many patients can achieve improved growth and quality of life, though careful monitoring of renal function and electrolytes remains essential.

Common questions about Bartter syndrome