Bartter syndrome E26.8

Group of renal diseases characterized by autosomal recessive inherited tubular dysfunction, with hypokalemic alkalosis, hypercalciuria, elevated plasma levels of renin and aldosterone, low blood pressure, and angiotensin II resistance of the vessels.

There are five genetic types of BS, but only two clinically distinguishable types:

• Antenatal or infantile Bartter syndrome (most with genetic types I, II, and IV) with hydramnios, prematurity, polyuria, dehydration, hypercalciuria, and nephrocalcinosis
• classic Bartter syndrome (mostly patients with genotype III, but some with genotype IV) with polyuria-polydipsia beginning in infancy, childhood, or adulthood, dehydration, and delayed length and weight gain. Urinary calcium levels are either normal or mildly elevated. Specific signs and symptoms include hearing impairment in Bartter syndrome type IV and hypocalcemia in BS type V.

The annual incidence is estimated at 1:830,000.

• Type I is defined by mutations in the SLC12A1 gene (chromosomal region 15q15-q21), which encodes the sodium-potassium-chloride cotransporter NKCC2.
• Type II of BS is defined by mutations in the KCNJ1 gene (11q21-q25), which encodes the potassium channel ROMK.
• Type III(classic type) is defined by mutations in the CLCNKB gene (1p36), which encodes a basolateral membrane chloride channel.
• Type IV is defined by mutations in the BSND gene (1p31), which encodes Barttin, a chloride channel subunit.
• Type V is inherited in an autosomal dominant manner and is caused by heterozygous activating mutations in the CASR gene (3q13.3-q21), which encodes a calcium receptor.

• Pseudo-Bartter syndrome (diuretic abuse, secret vomiting; frequent in cystic fibrosis)
• Gitelman syndrome
• Cystic fibrosis
• Celiac sprue.

Treatment consists of oral potassium supplementation, indomethacin and possibly potassium-sparing diuretics. Caution: In stress situations (additional diseases, surgical procedures, trauma), electrolyte blood levels may change very rapidly, requiring rapid and intensive intravenous treatment.

Follow-up of BS type III (classic type) in 77 patients revealed that 19 patients (25%) were diagnosed with chronic renal failure: one patient required hemodialysis and 4 patients underwent renal transplantation (Seys E et al. 2017).

1. Fulchiero R et al (2019) Bartter syndrome and Gitelman syndrome. Pediatr Clin North Am 66:121-134.
2. Gómez de la F CL et al (2019) Bartter syndrome: An infrequent tubulopathy of prenatal onset. Rev Chil Pediatr 90:437-442.
3. Seys E et al (2017) Clinical and Genetic Spectrum of Bartter Syndrome Type 3. J Am Soc Nephrol 28:2540-2552.