title: Early appearance of hypokalemia in Gitelman syndrome.
abstract: Inactivating mutations in the SLC12A3 gene that encodes the thiazide-sensitive co-transporter causes Gitelman syndrome. The main features of this syndrome include normal or low blood pressure, hypokalemia, metabolic alkalosis, hypomagnesemia, hypocalciuria, and hyperreninemia. These patients are at low risk for preterm birth and do not present with symptoms before school age. As a consequence, the condition is usually diagnosed in late childhood or in adult life. We report on four patients, two pairs of prematurely born twins, in whom hypokalemia was demonstrated early in life. In these children, a tendency towards hypokalemia was first noted during the third week of life. Overt hypokalemia subsequently appeared associated with normal blood pressure, hypochloremia, hyperreninemia, and an inappropriately high fractional excretion of potassium and chloride. Molecular biology studies failed to detect mutations in the SLC12A1, KCNJ1, and CLCNKB genes responsible for the Bartter syndromes type I, II and III, respectively. Compound heterozygous mutations in the SLC12A3 gene were detected in both pairs of twins: a frameshift mutation in exon 10 (c.1196_1202dup7bp), leading to the truncated protein p.Ser402X, and a missense mutation in exon 11, p.Ser475Cys (c.1424C>G) in the first pair; two missense mutations, p.Thr392Ile (c.1175C>T) in exon 9 and p.Ser615Leu in exon 15 (c.1844C>T), in the second pair. In conclusion, the diagnosis of Gitelman syndrome deserves consideration in infants with unexplained hypokalemia.
authors.affiliation: Department of Pediatrics, San Leopoldo Mandic Hospital, Largo Mandic 1, 23807, Merate-Lecco, Italy.
authors.forename: Fabiana
authors.initials: F
authors.lastname: Tammaro
authors.forename: Alberto
authors.initials: A
authors.lastname: Bettinelli
authors.forename: Donatella
authors.initials: D
authors.lastname: Cattarelli
authors.forename: Alessandra
authors.initials: A
authors.lastname: Cavazza
authors.forename: Carla
authors.initials: C
authors.lastname: Colombo
authors.forename: Marie-Louise
authors.initials: ML
authors.lastname: Syrén
authors.forename: Silvana
authors.initials: S
authors.lastname: Tedeschi
authors.forename: Mario G
authors.initials: MG
authors.lastname: Bianchetti
mesh_terms: D002675:Child, Preschool; D005260:Female; D053579:Gitelman Syndrome / Q000150:complications* / Q000235:genetics; D006801:Humans; D007008:Hypokalemia / Q000209:etiology*; D007231:Infant, Newborn; D007234:Infant, Premature; D008297:Male; D009154:Mutation; D011955:Receptors, Drug / Q000235:genetics; D064486:Solute Carrier Family 12, Member 3; D027981:Symporters / Q000235:genetics
chemical_list: D011955:Receptors, Drug; C578874:SLC12A3 protein, human; D064486:Solute Carrier Family 12, Member 3; D027981:Symporters