Bartter Syndrome
Basics
- Bartter syndrome and Bartter-like syndrome are a group of rare, autosomal recessive, salt-wasting nephropathies characterized by polyuria, hypokalemia, metabolic alkalosis, and normotension with hyperreninemic hyperaldosteronism (1).
- Traditionally, they have been divided into two main disorders according to where the defect is located in the renal tubule. However, more subtypes have been described with genetic classification (2).
- Bartter (furosemide type) has five subtypes, and Gitelman (thiazide type) has three subtypes; there are three combinations of the two (3).
Description
Bartter disorders have diverse genetic origins, with a common pathologic mechanism of a severe reduction in salt reabsorption by the thick ascending limb of Henle (TAL) and/or the distal convoluted tubule (DCT).
Epidemiology
Prevalence
Gitelman prevalence is calculated at 1:40,000. Heterozygote state in Caucasians: 1%
Etiology and Pathophysiology
- Bartter type is caused by inactivating mutations in one of several genes encoding membrane proteins in charge of transporting sodium (Na), chloride (Cl), potassium (K), and sometimes calcium (Ca) in the loop of Henle, where 25% of the filtered solute load is reabsorbed. This causes large urinary losses of Na, Cl, K, Mg, and Ca. It resembles the effect of large doses of furosemide, which results in hypovolemia with activation of the renin aldosterone system without any hypertension. According to which transporter is compromised, the disease will be more or less severe and it will start sooner or later. When it starts in utero, it causes polyhydramnios because of fetal polyuria. There is also secondary stimulation of prostaglandin E2 (PGE2) production with worsening of salt losses (2).
- In the Gitelman type, the inactivating mutations are in the DCT, where 5% of the filtered Na is reabsorbed. It resembles the effect of thiazides and causes urinary losses of Na, Cl, K, and Mg but not Ca. It is clinically less severe (2).
- The inactivating mutations in Bartter syndrome are in type I, the Na+-K-2Cl–cotransporter (SLC12A1 encoding NKCC2); in type II, the apical inward-rectifying K channel (KCNJ1 encoding ROMK); in type III, the basolateral Cl channel (ClCNK encoding ClC-Kb); and in type IV, the BSND, a protein that acts as an essential activator β-subunit for ClC-Ka and ClC-Kb Cl channels. Type V is a gain-of-function mutation in the extracellular Ca-sensing receptor (CaSR) that causes a variant with hypocalcemia (1,2).
- In Gitelman, the inactivating mutations are in the SLC12A3 gene encoding the thiazide-sensitive Na-Cl cotransporter or NCCT (2,4).
Genetics
Autosomal recessive
Risk Factors
Consanguinity
Commonly Associated Conditions
- Polyhydramnios, prematurity
- Nephrocalcinosis, rickets, growth retardation
- Hyperprostaglandin levels in Bartter syndrome (5)
- Sensorineural deafness, mental retardation in type IV
- Cardiac problems
- Gallstones
- Constipation
- Hypertension later in life
- Chondrocalcinosis in Gitelman syndrome due to hypomagnesemia (5)
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Citation
Domino, Frank J., et al., editors. "Bartter Syndrome." 5-Minute Clinical Consult, 33rd ed., Wolters Kluwer, 2025. Medicine Central, im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/816177/all/Bartter_Syndrome.
Bartter Syndrome. In: Domino FJF, Baldor RAR, Golding JJ, et al, eds. 5-Minute Clinical Consult. Wolters Kluwer; 2025. https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/816177/all/Bartter_Syndrome. Accessed December 9, 2024.
Bartter Syndrome. (2025). In Domino, F. J., Baldor, R. A., Golding, J., & Stephens, M. B. (Eds.), 5-Minute Clinical Consult (33rd ed.). Wolters Kluwer. https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/816177/all/Bartter_Syndrome
Bartter Syndrome [Internet]. In: Domino FJF, Baldor RAR, Golding JJ, Stephens MBM, editors. 5-Minute Clinical Consult. Wolters Kluwer; 2025. [cited 2024 December 09]. Available from: https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/816177/all/Bartter_Syndrome.
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