Bartter Syndrome

Bartter syndrome is a rare autosomal recessive disorder characterized by hypokalemia, metabolic alkalosis, secondary hyperreninemia and hyperaldosteronism, and, in some patients, hypomagnesemia. Prevalence is estimated to be one in a million individuals. Severe cases cause growth retardation.

Several different channels regulate sodium chloride reabsorption in the thick ascending limb of the loop of Henle in the kidney. Cl-channel kidney B (ClC-Kb) is the most important chloride channel and is located in the basolateral membrane of the thick ascending limb in the medulla of the kidney. Another chloride channel, ClC-Ka, may have redundant functionality. A small protein beta-subunit, named barttin, must interact with each of these chloride channels for them to function appropriately. Bartter Syndrome is caused by mutations in any one of the genes that regulates sodium chloride reabsorption. The phenotype of Bartter Syndrome is highly variable, ranging from antenatal onset to a picture resembling Gitelman Syndrome. Five subtypes have been described based on the underlying mutation: 

Type 1, SLC12A2 [solute carrier family 12 (sodium/potassium/chloride transporter), member 2]

Type 2, KCNJ1 (potassium channel, inwardly rectifying subfamily J, member 1)  

Type 3, CLCNKB (chloride channel, voltage-sensitive Kidney B)  

Type 4, BSND (barttin CLCNK-type chloride channel accessory β subunit)  

Type 5, CASR (calcium-sensing receptor) 

Defective sodium and potassium reabsorption in the thick ascending limb of the nephron results in reduced calcium reabsorption and excessive delivery of calcium to more distal parts of the kidney. This explains the occurrence of nephrocalcinosis. 

Laboratory tests that are used to diagnose these disorders include blood tests for plasma electrolytes, magnesium, renin, and aldosterone. Urine tests include prostaglandin E2, urine electrolyes, calcium, and magnesium. Molecular genetic testing can identify the variants associated with each subtype of Bartter syndrome. 

References

Bartter Syndrome, National Organization of Rare Disorders, https://rarediseases.org/rare-diseases/bartters-syndrome/#diagnosis

Cunha TDS, Heilberg IP. Bartter syndrome: causes, diagnosis, and treatment. Int J Nephrol Renovasc Dis. 2018 Nov 9;11:291-301. doi: 10.2147/IJNRD.S155397.