Subtypes of Bartter Syndrome*
Subtype | Gene (Protein)† | Age of Onset | Clinical Features |
|---|---|---|---|
I | SLC12A1 (NKCC2)† | Antenatal/neonatal | Polyhydramnios, prematurity, hypokalemia/alkalosis, polyuria, hypercalciuria, nephrocalcinosis |
II | KCNJ1 (ROMK1)† | Antenatal/neonatal | Similar to type I |
III | CLCNKB (ClC-Kb)† | Later onset (childhood) | Similar to type I, may be less severe Some children present with Gitelman phenotype as ClC-Kb found in the distal convoluted tubule and in the connecting tubule |
IV | BSND (Barttin)† | Antenatal/neonatal | Similar to type I, nephrocalcinosis less common Associated with sensorineural hearing loss |
IVb | CLCNKA (ClC-Ka)† and CLCNKB (ClC-Kb)† | Antenatal/neonatal | Similar to type IV Associated with sensorineural hearing loss |
V | CASR (CaSR)† | Later onset | Due to CaSR gain of function, which may reduce ROMK and NKCC2 activity |
* Bartter classification: Gene abnormalities alter sodium chloride and potassium transport in the thick ascending limb of the loop of Henle. † Protein abbreviations: Barttin = beta subunit of ClC-Ka and ClC-Kb; CaSR = calcium-sensing receptor; ClC-Kb = basolateral chloride channel kidney B; ClC-Ka = basolateral chloride channel kidney A; NKCC2 = Na-K-2Cl channel; ROMK = luminal potassium channel. | |||