Bartter syndrome causes

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Tayyaba Ali, M.D.[2]

Overview

Bartter syndrome can be caused by mutations in at least five genes. Mutations in the SLC12A1 gene cause type I. Type II results from mutations in the KCNJ1 gene. Mutations in the CLCNKB gene are responsible for type III. Type IV can result from mutations in the BSND gene or from a combination of mutations in the CLCNKA and CLCNKB genes as shown in the table. Aminoglycoside can induce Bartter syndrome presenting with severe hypokalemia, metabolic alkalosis, and profound systemic manifestations.

Causes

Bartter syndrome can be caused by mutations in at least five genes.
Mutations in the SLC12A1 gene cause type I. Type II results from mutations in the KCNJ1 gene. Mutations in the CLCNKB gene are responsible for type III. Type IV can result from mutations in the BSND gene or from a combination of mutations in the CLCNKA and CLCNKB genes as shown in the table.
The genes associated with Bartter syndrome play important roles in normal kidney function. The proteins produced from these genes are involved in the kidneys’ reabsorption of salt.
Mutations in any of the five genes impair the kidneys’ ability to reabsorb salt, leading to the loss of excess salt in the urine (salt wasting). Abnormalities of salt transport also affect the reabsorption of other charged atoms (ions), including potassium and calcium. The resulting imbalance of ions in the body leads to the major features of Bartter syndrome.^[1]

Classification of Bartter syndrome on the basis of both genotype and phenotype^[2]^[3]
Disorder	Gene affected	Gene product	Clinical presentation (phenotype)
Bartter syndrome type I	SLC12A1	NKCC2	Antenatal Bartter syndrome (hyperprostaglandin E syndrome)
Bartter syndrome type II	KCNJ1	ROMK	Antenatal Bartter syndrome
Bartter syndrome type III	ClC-Kb	CLC-Kb	Hypochloremia, mild hypomagnesemia, failure to thrive in infancy
Bartter syndrome type IVA	BSND	Barttin (B-subunit of CLC-Ka and CLC-Kb)	Antenatal Bartter syndrome (hyperprostaglandin E syndrome) and sensorineural deafness
Bartter syndrome type IVB	ClC-Ka and ClC-Kb	CLC-Ka and CLC-Kb	Antenatal Bartter syndrome (hyperprostaglandin E syndrome) and sensorineural deafness
Bartter syndrome type V	CaSR gene	CaSR	Bartter syndrome with hypocalcemia

In some patients with Bartter syndrome, the genetic cause of the disorder is unknown. Researchers are searching for additional genes that may be associated with this condition.^[1]
Aminoglycoside can induce Bartter syndrome presenting with severe hypokalemia, metabolic alkalosis, and profound systemic manifestations.^[4]

References

Overview