Bartter Syndrome

Bartter syndrome is a group of inherited tubulopathies from defective sodium chloride reabsorption in the thick ascending limb of the loop of Henle, causing salt wasting, hypokalaemic metabolic alkalosis and hyperreninaemic hyperaldosteronism with normal blood pressure.

• Types:
  • Type I (SLC12A1, NKCC2): antenatal/neonatal, polyhydramnios.
  • Type II (KCNJ1, ROMK): antenatal, transient neonatal hyperkalaemia.
  • Type III (CLCNKB): classic Bartter, presents in infancy to childhood; overlap with Gitelman.
  • Type IVa (BSND, with deafness), IVb (CLCNKA and CLCNKB digenic).
  • Type V (CASR gain of function): hypocalcaemia with Bartter features.
  • MAGED2: transient antenatal Bartter.
• Prevalence about 1 per million.
• Pathophysiology mimics chronic loop diuretic use: hypercalciuria, nephrocalcinosis (types I, II, IV), hyperprostaglandin E2 production.
• Complications: growth retardation, nephrocalcinosis, CKD, sensorineural deafness (type IV).

• Antenatal forms: polyhydramnios, prematurity, severe neonatal dehydration, failure to thrive, fever, vomiting, polyuria.
• Classic: polyuria, polydipsia, salt craving, muscle weakness, cramps, constipation, growth failure, tetany (type V, hypocalcaemia).
• Normal or low blood pressure despite high renin.
• Sensorineural deafness (type IV).
• Dysmorphic triangular face, prominent forehead in infants.

• Hypokalaemia (2 to 3 mmol/L), metabolic alkalosis, hypochloraemia, high renin and aldosterone, normal blood pressure.
• Urine chloride high (over 20 mmol/L), urinary calcium high (types I, II, IV), low to normal magnesium (type III may be low).
• Exclude surreptitious diuretic use (urine diuretic screen), vomiting (low urine chloride), cystic fibrosis (sweat chloride), Gitelman syndrome (hypomagnesaemia, hypocalciuria), Liddle syndrome (hypertension).
• Genetic testing for panel (SLC12A1, KCNJ1, CLCNKB, BSND, CASR, MAGED2).
• Renal ultrasound for nephrocalcinosis; audiology; growth assessment; ECG.
• Tubular function: fractional excretion of chloride, response to furosemide stimulation (blunted) or hydrochlorothiazide test (differentiates from Gitelman).

• Potassium chloride supplementation 3 to 10 mmol/kg/day (adults 60 to 200 mmol/day) in divided doses, sustained-release or liquid; sodium chloride 3 to 5 mmol/kg/day (or free salt intake) with fluid.
• Indomethacin 1 to 4 mg/kg/day (maximum 5 mg/kg/day) in 3 to 4 divided doses (or ibuprofen 20 to 30 mg/kg/day) to reduce prostaglandin E2, improves growth and polyuria; monitor for gastrointestinal side effects and kidney function; in neonates use caution (necrotising enterocolitis).
• Potassium-sparing agents: spironolactone 1.5 to 3 mg/kg/day, eplerenone, amiloride 0.3 to 0.4 mg/kg/day to increase potassium; ACE inhibitors (cautious).
• Magnesium supplementation when low.
• Treat nephrocalcinosis (limit hypercalciuria; thiazide not appropriate for ongoing salt wasting but sometimes used; potassium citrate).
• Growth hormone in persistent growth failure; hearing aids/cochlear implant (type IV).
• Antenatal Bartter: amnioreduction, indomethacin in pregnancy (avoid after 32 weeks), neonatal intensive care.
• Monitor electrolytes, renal function, growth, nephrocalcinosis, and audiology; renal transplantation for ESKD.
• Genetic counselling.