PURPOSE OF REVIEW: This review describes recent advances in our understanding of 
the genetic heterogeneity, pathophysiology and treatment of Bartter syndrome, a 
group of autosomal recessive disorders that are characterized by markedly 
reduced or absent salt transport by the thick ascending limb of Henle. 
Consequently, individuals with Bartter syndrome exhibit renal salt wasting and 
lowered blood pressure, hypokalemic metabolic alkalosis and hypercalciuria with 
a variable risk of renal stones.
RECENT FINDINGS: Previously, three genes (SLC12A2, the sodium-potassium-chloride 
co-transporter; KCNJ1, the ROMK potassium ion channel; ClC-Kb, the basolateral 
chloride ion channel) had been identified as causing antenatal and 'classic' 
Bartter syndrome. Two additional genes have now been identified. Barttin is a 
beta-subunit that is required for the trafficking of CLC-K (both ClC-Ka and 
ClC-Kb) channels to the plasma membrane in both the thick ascending limb and the 
marginal cells in the scala media of the inner ear that secrete potassium 
ion-rich endolymph. Loss-of-function mutations in barttin thus cause Bartter 
syndrome with sensorineural deafness. In addition, severe gain-of-function 
mutations in the extracellular calcium ion-sensing receptor can result in a 
Bartter phenotype because activation of this G protein-coupled receptor inhibits 
salt transport in the thick ascending limb (a furosemide-like effect).
SUMMARY: Five genes have been identified as causing Bartter syndrome (types 
I-V), with the unifying pathophysiology being the loss of salt transport by the 
thick ascending limb. Phenotypic differences in Bartter types I-V relate to the 
specific physiological roles of the individual genes in the kidney and other 
organ systems.