Bartter Syndrome, Type 3 (CLCNKB)
Bartter syndrome type III is an autosomal recessive disorder caused by pathogenic variants in the gene CLCNKB. This gene encodes a chloride channel called ClC-Kb which are located predominantly in the kidneys. ClC-Kb helps kidneys reabsorb salt from urine back into the bloodstream. Pathogenic variants in CLCNKB eliminate or reduce production of chloride channels, inhibiting the kidney’s ability to reabsorb salt normally and leading to salt-wasting and ion imbalance. The onset of this condition occurs in childhood and the severity of symptoms varies. Salt-wasting may lead to dehydration, constipation, and polyuria. Ion imbalance can lead to hypercalcemia, which can cause osteopenia and nephrocalcinosis. Affected individuals tend to have hyperkalemia, which can manifest as muscle weakness, cramping, and fatigue. Though rare, renal failure may occur. Life expectancy may be reduced depending on the severity of symptoms. Complete loss-of-function variants and missense variants resulting in very little residual activity have been shown to result in a younger age of onset (PMID:28381550). The prevalence of this condition is unknown.
For information about carrier frequency and residual risk, please see the residual risk table.