Autosomal recessive transmitted secondary hyperaldosteronism with normal blood pressure and polyuria. Peculiar facies is common. Do not confuse with ☞Schwarz-Bartter Syndrome (also called syndrome of inappropriate antidiuretic hormone secretion [SIADH]).
Hypokalemic Alkalosis with Hypercalciuria Aldosteronism-Normal Blood Pressure Syndrome; Hypokalemic Alkalosis Juxtaglomerular Hyperplasia Syndrome; Hyperprostaglandin E Syndrome (included).
Named after the American physician Frederic Crosby Bartter, who described this syndrome in 1962. However, 2 years earlier, P. Pronove had already described the disorder in a 5-year-old boy.
The exact incidence is unknown, but is estimated to be approximately 1:1,000,000 to 10 in 1,000,000 live births. No racial or sexual predilection has been reported.
Autosomal recessive with parental consanguinity being a risk factor. The mutations (see “Classification”) result in defects of sodium, chloride, and potassium reabsorption mainly in the thick ascending limb of Henle’s loop.
Based on clinical and biochemical findings and confirmed by genetic testing.
Based on the underlying genetic defect, five types of BS can be distinguished:
(Antenatal) BS Type 1 (BS1): Caused by mutations in SLC12A1 (Solute carrier family 12 (sodium/potassium/chloride transporters), member 1) gene mapped to chromosome 15q21.1 encoding the Na-K-Cl cotransporter 2 (NKCC2). The defect is located in the thick ascending limb of Henle’s loop.
(Antenatal) BS Type 2 (BS2): Caused by mutations in the KCNJ1 (Potassium inwardly rectifying channel, subfamily J, member 1 or ROMK1 [Renal outer-medullary potassium channel]) gene located on chromosome 11q24.3, which encodes for the renal outer-medullary potassium channel. The defect is located in the thick ascending limb of Henle’s loop and the cortical collecting duct.
(Classic) BS Type 3 (BS3): Caused by mutations in the CLCNKB (Chloride channel, kidney, B) gene mapped to chromosome 1p36, which encodes for the chloride voltage-gated channel KB. The defect is located in the thick and the thin ascending limb of Henle’s loop, the cortical collecting duct, and the distal convoluted tubule.
(Neonatal) BS Type 4A (BS4A): Caused by mutations in BSND (Barttin CLCNK type accessory beta subunit) on chromosome 1p32.3, which encodes for Barttin, a protein subunit found in both basolateral renal chloride channels A and B (CLCNKA and CLCNKB) often associated with deafness. The defect is located in the thick ascending limb of Henle’s loop, the cortical collecting duct, and the distal convoluted tubule.
(Neonatal) BS Type 4B (BS4B): Caused by simultaneous mutations in the CLCNKA (Chloride Channel, Kidney, A) and CLCNKB (Chloride Channel, Kidney, B) genes located on chromosome 1p36.13.
(Antenatal, transient) BS Type 5 (BS5): Associated with hypocalcemia and caused by mutations of the extracellular calcium sensing receptor (CASR) gene located on chromosome 3q13.3, which encodes for both the renal and parathyroidal ...