title: Autosomal dominant hypocalcemia with mild type 5 Bartter syndrome.
abstract: Type 5 Bartter syndrome has been recently defined as a Bartter syndrome due to the most activating mutations of the calcium-sensing receptor (CaSR). It has been attributed to the inhibition exerted by CaSR activity on sodium transport in the thick ascending limb of the loop of Henle (TALH). Two monozygotic twin sisters (T1 and T2) with autosomal dominant hypocalcemia (ADH) due to a nonconservative activating CaSR mutation in the extracellular domain (K29E) were studied. They developed a Bartter-like syndrome characterized by a mild phenotype: hypokalemia occurred only at the age of 22 years; it was corrected with small doses of oral potassium in one twin, while the other twin needed no potassium supplements to maintain borderline levels of plasma potassium; alkalosis was absent; plasma renin and aldosterone production were not markedly activated. Furthermore, the natriuretic response to furosemide, a inhibitor of sodium reabsorption in the TALH, was conserved in both twins. The K29E mutation was previously reported as one of the most activating mutations of the CaSR gene leading to a very marked increase in CaSR sensitivity to calcium ions. These findings confirm that Bartter syndrome is typically associated with ADH provided that the underlying mutation of CaSR is able to produce a conspicuous gain of function. However, the phenotype of type 5 Bartter syndrome may manifest with variable severity, not directly related with the in vitro potency of the CaSR activating mutation.
authors.affiliation: Nephrology and Dialysis Unit, IRCCS San Raffaele Hospital, Vita Salute University, Milan, Italy. vezzoli.giuseppe@hsr.it
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Vezzoli
authors.forename: Teresa
authors.initials: T
authors.lastname: Arcidiacono
authors.forename: Vera
authors.initials: V
authors.lastname: Paloschi
authors.forename: Annalisa
authors.initials: A
authors.lastname: Terranegra
authors.forename: Rita
authors.initials: R
authors.lastname: Biasion
authors.forename: Giovanna
authors.initials: G
authors.lastname: Weber
authors.forename: Stefano
authors.initials: S
authors.lastname: Mora
authors.forename: Marie Louise
authors.initials: ML
authors.lastname: Syren
authors.forename: Domenico
authors.initials: D
authors.lastname: Coviello
authors.forename: Daniele
authors.initials: D
authors.lastname: Cusi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Bianchi
authors.forename: Laura
authors.initials: L
authors.lastname: Soldati
mesh_terms: D000328:Adult; D001477:Bartter Syndrome / Q000235:genetics*; D004200:Diseases in Twins; D005260:Female; D006801:Humans; D006996:Hypocalcemia / Q000209:etiology / Q000235:genetics*; D009154:Mutation; D044169:Receptors, Calcium-Sensing / Q000235:genetics* / Q000502:physiology
chemical_list: C095550:CASR protein, human; D044169:Receptors, Calcium-Sensing