Clinical presentation of genetically defined patients with hypokalemic salt-losing tubulopathies

Differential diagnosis of Bartter syndrome, Gitelman syndrome, and pseudo–Bartter/Gitelman syndrome based on clinical characteristics

“…We performed genetic tests based on the BS/GS genetic analysis algorithm proposed by Peters et al 21 and assessed the patients' clinical findings and biochemical parameters. Among these 190 patients, 21 with genetically defined type I, II, or IV BS were excluded from this study, together with 6 patients with only one mutant allele in CLCNKB or SLC12A3.…”

“…Antenatal BS is usually easy to diagnose because patients present with typical symptoms, such as polyhydramnios, low birth weight, or failure to thrive, during the antenatal or neonatal period. 5,21 By contrast, the clinical manifestations of type III BS and GS may vary and resemble each other. 7,[11][12][13] Furthermore, p-BS/GS is difficult to distinguish from type III BS or GS because its clinical features match those of the latter two diseases.…”

Clinical and Genetic Spectrum of Bartter Syndrome Type 3

“…The 11 phenotype was ante/neonatal Bartter Syndrome (polyhydramnios or diagnosis in the first 12 month of life) in 30% of cases, classic Bartter Syndrome (diagnosis during childhood, 13 hypercalciuria and/or polyuria) in 45% and Gitelman-like syndrome (fortuitous discovery of 14 hypokalemia with hypomagnesemia and/or hypocalciuria in childhood or adulthood) in 25%. 15 Nine of the 10 mutations expressed in vitro decreased or abolished chloride conductance. 16 Severe (large deletions, frameshift, nonsense, and essential splicing) and missense mutations 17 resulting in poor residual conductance were associated with younger age at diagnosis.…”

“…23 The first BS3 patients described had a clinical phenotype corresponding to CBS 7 . 24 Considerable phenotypic variability has since been described: CLCNKB mutations can also 25 6 underlie the ABS, neonatal BS (NBS), and Gitelman-like (GLS) phenotypes [13][14][15] families. In all cases, parents were heterozygous for the homozygous mutation detected in the 1 proband or for one of the two mutations detected in compound heterozygous probands.…”

“…Median follow-up was eight years and was similar in the three groups. The main 15 treatments administered to these patients were NaCl and KCl supplementation and non- 16 steroidal anti-inflammatory drugs (NSAIDs, mainly indomethacin). The main adverse effects 17 were abdominal pain (n=5), weight gain (n=1), esophagitis (n=1), and diarrhea (n=1).…”