Autosomal dominant hypocalcemia with mild type 5 Bartter syndrome.
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.
Vezzoli
Giuseppe
G
Nephrology and Dialysis Unit, IRCCS San Raffaele Hospital, Vita Salute University, Milan, Italy. vezzoli.giuseppe@hsr.it
Arcidiacono
Teresa
T
Paloschi
Vera
V
Terranegra
Annalisa
A
Biasion
Rita
R
Weber
Giovanna
G
Mora
Stefano
S
Syren
Marie Louise
ML
Coviello
Domenico
D
Cusi
Daniele
D
Bianchi
Giuseppe
G
Soldati
Laura
L
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
C095550:CASR protein, human; D044169:Receptors, Calcium-Sensing