Bartter syndrome

BS is a rare inherited salt-losing renal tubular disorder characterised by hypokalemia, metabolic alkalosis, hyperreninemia, hyperaldosteronism, hypercalciuria, polyuria, and polydipsia, accompanied by normal or low blood pressure. Clinical expression is highly variable and gene-dependent. Severe antenatal and neonatal forms of BS typically present with polyhydramnios, prematurity, postnatal polyuria, dehydration and failure to thrive, whereas the classic form presents in infancy or childhood with milder salt wasting, growth retardation and muscular symptoms. Sensorineural hearing loss is a defining feature of the antenatal type IVa form. Long-term outcome is not uniformly benign: chronic kidney disease develops in approximately 30% of patients with BS.

The prevalence of BS is reported to be about 1 in 1,000,000, making it far less common than Gitelman syndrome.

BS is caused by biallelic germline pathogenic variants in genes encoding apical and basolateral ion-transport proteins of the thick ascending limb of the loop of Henle (TAL), leading to impaired NaCl reabsorption with consecutive secondary hyperaldosteronism. Five causative genes are established: CLCNKB, which encodes the basolateral chloride channel CLC-Kb, the most commonly affected gene, underlying the classic form (type III); SLC12A1, which encodes the Na-K-2Cl cotransporter (NKCC2) in the apical membrane of epithelial cells in the TAL, and KCNJ1 , which encodes the renal outer medullary potassium (ROMK) channel, causing antenatal/neonatal BS types I and II, respectively; BSND, encoding barttin, which is an essential subunit for CIC-Ka and CIC-Kb channels, causing antenatal type IVa with sensorineural deafness; and MAGED2 (melanoma-associated antigen D2), underlying an X-linked transient antenatal form.

BS is inherited in an autosomal recessive manner, except for the MAGED2-related transient antenatal form, which follows X-linked inheritance. For autosomal recessive forms, the recurrence risk for siblings of an affected child is 25%. Prenatal molecular testing is technically possible once the familial pathogenic variants have been identified.

The diagnosis rests on a characteristic biochemical signature: hypokalaemic hypochloraemic metabolic alkalosis with elevated plasma renin and aldosterone activity, normal to low blood pressure and renal salt wasting. Supportive findings include hypercalciuria (notably in types I and II) and elevated prostaglandin E2 excretion in antenatal forms. Nephrocalcinosis on renal ultrasound is characteristic of antenatal BS types I and II, and polyhydramnios on prenatal ultrasound is a hallmark of the antenatal forms.

Main differential diagnoses include:

• : later-onset salt-losing tubulopathy with hypomagnesaemia and hypocalciuria rather than the hypercalciuria characteristic of antenatal Bartter; SLC12A3
• Pseudo-Bartter syndrome (cystic fibrosis-related, or from surreptitious diuretic use, laxative abuse or chronic vomiting): acquired hypokalaemic hypochloraemic alkalosis without a primary tubular ion-transport defect; CFTR or no monogenic cause
• EAST/SeSAME syndrome: Bartter-like salt-losing tubulopathy combined with epilepsy, ataxia and sensorineural deafness; KCNJ10

• Establishing the diagnosis: molecular genetic testing confirms the clinical diagnosis at the molecular level, distinguishes the genetic subtype and resolves the differential against phenotypically overlapping tubulopathies.
• Specific and individualized surveillance: identification of the causative gene supports gene-specific surveillance, including monitoring for progression to chronic kidney disease.
• Family member testing: once the familial pathogenic variants are known, testing of at-risk relatives allows clarification of carrier status and informs reproductive counselling.

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• Konrad M, Nijenhuis T, Ariceta G, Bertholet-Thomas A, Calo LA, Capasso G, et al. Diagnosis and management of Bartter syndrome: executive summary of the consensus and recommendations from the European Rare Kidney Disease Reference Network Working Group for Tubular Disorders. Kidney Int. 2021;99(2):324-335. PMID: .
• Bokhari SRA, Zulfiqar H, Rauf N, et al. Bartter syndrome. [Updated 2026 Jan 31]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2026. Available from:
• Palazzo V, Raglianti V, Landini S, Cirillo L, Errichiello C, Buti E, et al. Clinical and genetic characterization of patients with Bartter and Gitelman syndrome. Int J Mol Sci. 2022;23(10):5641. PMID: .