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 Henle's loop. The most important chloride channel in the basolateral membrane of the medullary thick ascending limb of Henle's loop is Cl-channel kidney B (ClC-Kb). 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 these genes that regulate 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 TAL results in reduced calcium reabsorption and excessive delivery of calcium to more distal parts of the nephron. This explains the occurrence of nephrocalcinosis.
