Phenotypic variability in Bartter syndrome type I

Alberto Bettinelli, Sonia Ciarmatori, Layla Cesareo, Silvana Tedeschi, Giuseppe Ruffa, Aldo Claris Appiani, Augusto Rosini, Gianpaolo Grumieri, Bruno Mercuri, Michele Sacco, Giovanna Leozappa, Silvana Binda, Milvia Cecconi, Carla Navone, Cristina Curcio, Marie Louise Syren, Giorgio Casari

Research output: Contribution to journalArticle


Limited phenotypic variability has been reported in patients with Bartter syndrome type I, with mutations in the Na-K-2Cl cotransporter gene (BSC). The diagnosis of this hereditary renal tubular disorder is usually made in the antenatal-neonatal period, due to the presence of polyhydramnios, premature delivery, hypokalemia, metabolic alkalosis, hypercalciuria, and nephrocalcinosis. Among nine children with hypercalciuria and nephrocalcinosis, we identified new mutations consistent with a loss of function of the mutant allele of the BSC gene in five. Three of the five cases with BSC gene mutations were unusual due to the absence of hypokalemia and metabolic alkalosis in the first years of life. The diagnosis of incomplete distal renal tubular acidosis was considered before molecular evaluation. Three additional patients with hypokalemia and hypercalciuria, but without nephrocalcinosis in the first two and with metabolic acidosis instead of alkalosis in the third, were studied. Two demonstrated the same missense mutation A555T in the BSC gene as one patient of the previous group, suggesting a single common ancestor. The third patient presented with severe hypernatremia and hyperchloremia for about 2 months, and a diagnosis of nephrogenic diabetes insipidus was hypothesized until the diagnosis of Bartter syndrome type I was established by molecular evaluation. We conclude that in some patients with Bartter syndrome type I, hypokalemia and/or metabolic alkalosis may be absent in the first years of life and persistent metabolic acidosis or hypernatremia and hyperchloremia may also be present. Molecular evaluation can definitely establish the diagnosis of atypical cases of this complex hereditary tubular disorder, which, in our experience, may exhibit phenotypic variability.

Original languageEnglish
Pages (from-to)940-945
Number of pages6
JournalPediatric Nephrology
Issue number10-11
Publication statusPublished - Sep 2000



  • Bartter syndrome
  • Bumetanide-sensitive cotransporter gene
  • Hypercalciuria
  • Hypokalemia
  • Metabolic alkalosis
  • Nephrocalcinosis
  • Nephrogenic diabetes insipidus

ASJC Scopus subject areas

  • Nephrology
  • Pediatrics, Perinatology, and Child Health

Cite this

Bettinelli, A., Ciarmatori, S., Cesareo, L., Tedeschi, S., Ruffa, G., Appiani, A. C., Rosini, A., Grumieri, G., Mercuri, B., Sacco, M., Leozappa, G., Binda, S., Cecconi, M., Navone, C., Curcio, C., Syren, M. L., & Casari, G. (2000). Phenotypic variability in Bartter syndrome type I. Pediatric Nephrology, 14(10-11), 940-945.