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Background Patients with Gitelman syndrome, a hereditary salt-wasting tubulopathy, have loss-of-function mutations in the SLC12A3 gene coding for the thiazide-sensitive sodium chloride co-transporter in the distal convoluted tubule. Since the bulk of filtered phosphate is reabsorbed in the proximal tubule, renal phosphate wasting is considered exceptional in Gitelman syndrome. Methods We investigated the renal handling of inorganic phosphate in 12 unselected Italian patients affected with Gitelman syndrome (5 females and 7 males, aged 6.0-18 years, median age 12 years) and in 12 healthy subjects matched for gender and age (controls). The diagnosis of Gitelman syndrome among the patients had been made clinically and confirmed by molecular biology studies. Results The biochemical hallmarks of Gitelman syndrome, namely hypochloremia, hypokalemia, hypomagnesemia, increased urinary excretion of sodium, chloride, potassium and magnesium and reduced urinary excretion of calcium, were present in the 12 patients. In addition, both the plasma inorganic phosphate concentration (median and interquartile range: 1.28 [1.12-1.36] vs. 1.61 [1.51-1.66)] mmol/L) and the maximal tubular reabsorption of inorganic phosphate (1.08 [0.99-1.22] vs. 1.41 [1.38-1.47] mmol/L) were significantly lower (P Conclusions The results of our case-control study disclose a hitherto unrecognized tendency towards renal phosphate wasting with mild to moderate hypophosphatemia in Gitelman syndrome. Keywords Gitelman syndrome * Hypokalemia * Hypomagnesemia * Hypophosphatemia * Renal phosphate wasting, Introduction The kidney plays a key role in the maintenance of inorganic phosphate homeostasis [1, 2]. Since the bulk of filtered inorganic phosphate is reabsorbed in the proximal tubule, renal [...]

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. Keywords Gitelman syndrome * Bartter syndrome * Hypokalemia * Hypomagnesemia * Preterm neonate, Introduction Inactivating mutations in the SLC12A3 gene that encodes the thiazide-sensitive sodium chloride co-transporter cause Gitelman syndrome (OMIM 263800), an autosomalrecessive renal tubular disorder whose features include hypokalemia, metabolic alkalosis, [...]

Byline: Cristina Malafronte (1), NicolA2 Borsa (3), Silvana Tedeschi (3), Marie-Louise Syren (4), Sara Stucchi (2), Mario Giovanni Bianchetti (5), Felice Achilli (1), Alberto Bettinelli (2,6) Keywords: Classic Bartter disease; Hypokalemia; Cardiac arrhythmias; Holter monitoring; QT interval Abstract: We report a young girl with classic Bartter disease (type III) with severe hypokalemia (a$?2.0 mmol/l) who developed a prolonged heart rate-corrected QT interval of 510 ms (upper reference 430 ms) and ST segment depression in all leads. Holter electrocardiography was performed (with a plasma potassium level of 2.0 mmol/l) and it disclosed a stable sinus rhythm, a prolonged correct QT interval, more-evident ST segment depression during an increase in heart rate, a few single premature ventricular complexes, and nocturnal conduction abnormalities such as second-degree atrioventricular block 2:1. In the light of these results, the treatment was modified by increasing indomethacin from 1.5 to 3 mg/kg per day and adding spironolactone at a dose of 5 mg/kg per day. After 10 days, plasma potassium levels increased to 2.7 mmol/l and electrocardiographic abnormalities regressed. No other cardiac abnormalities were noted when the serum potassium was maintained &gt 2.5 mmol/l. In conclusion, this case report supports the link between arrhythmic events and chronic renal hypokalemic alkalosis in renal tubular disorders. We highlight the importance of standardizing the use of rest electrocardiography and 24-h Holter monitoring to diagnose arrhythmic events in children with severe hypokalemic renal disorders, especially in those with a plasma potassium &lt 2.5 mmol/l. The importance of beginning early medical treatment, to improve plasma potassium levels and reverse cardiac abnormalities, is emphasized. Author Affiliation: (1) Department of Cardiology, San Leopoldo Mandic Hospital, Merate, Lecco, Italy (2) Department of Pediatrics, San Leopoldo Mandic Hospital, Merate, Lecco, Italy (3) Molecular Genetics Laboratory, Istituti Clinici Perfezionamento, Milan, Italy (4) Department of Pediatrics and Neonatology, University of Milan, Italy (5) Department of Pediatrics, San Giovanni Hospital, Bellinzona, Switzerland (6) Department of Pediatrics, San Leopoldo Mandic Hospital, 23807, Merate, Lecco, Italy Article History: Registration Date: 21/07/2004 Received Date: 11/05/2004 Accepted Date: 02/07/2004 Online Date: 28/08/2004