Gitelman syndrome: clinical presentation and genetic analysis of 27 patients with hypokalemia caused by renal potassium wasting

Anne-Sophie Balavoine; Pierre Bataille; Philippe Vanhille; Raymond Azar; Francois Glowacki; Rosa Vargas-Poussou; Xavier Jeunemaitre; Jean-Louis Wemeau; Marie-Christine Vantyghem

P17

Prev Next

Section Contents Cite

Endocrine Abstracts (2009) 20 P17

ECE2009 Poster Presentations Adrenal (54 abstracts)

Gitelman syndrome: clinical presentation and genetic analysis of 27 patients with hypokalemia caused by renal potassium wasting

Anne-Sophie Balavoine ¹ , Pierre Bataille ² , Philippe Vanhille ³ , Raymond Azar ⁴ , François Glowacki ¹ , Rosa Vargas-Poussou ⁵ , Xavier Jeunemaitre ⁵ , Jean-Louis Wémeau ¹ & Marie-Christine Vantyghem ¹

Err

Author affiliations

¹CHRU, Lille, France; ²Centre hospitalier, Boulogne sur mer, France; ³Centre hospitalier, Valenciennes, France; ⁴Centre hospitalier, Dunkerque, France; ⁵HEGP, Paris, France.

Gitelman syndrome (GS) is a recessive salt loosing tubulopathy caused by mutations in the SLC12A3 gene encoding the thiazide-sensitive Na⁺-Cl⁻ cotransporter, and characterized by secondary hyperaldosteronism, hypokalemic alkalosis, hypomagnesemia and hypocalciuria.

The aim: Of the work was to investigate 27 adult patients with hypokalemia due to renal potassium wasting after exclusion of diuretics abuse, vomiting or diarrhea.

Methods: Clinical and biological data were recorded, and genetic analysis of SLC12A3 gene performed for each patient.

Results: Of 15 patients had two pathogenic mutations of SLC12A3 defining a true GS, two patients one single mutation, and nine no pathogenic mutation, but gene polymorphism in 6/9 cases. Patients with true GS were 35±15 years old at time of diagnosis. Symptoms (dizziness, paresthesia, tetany or nycturia) were present in 60% of cases. Complications of GS were found in five patients: two with chondrocalcinosis, two with growth delay, and one with syncope related to cardiac arrhythmia. Four patients had high blood pressure, while GS is usually associated with low blood pressure. All patients with true GS had hypokalemia (mean±S.E.M.: 2.8±0.3 mEq/l) and hyperreninism (except for one patient), while hypomagnesemia (absent in 8/15 patients) and hypocalciuria (absent in 2/7 explored patients) were inconstant. Hypokalemia was mild in patients without pathogenic mutation of SLC12A3: 3.5±0.3 mEq/l, and hyperreninism lacking in most cases. Follow-up of patients with true GS during 9±6 years was marked by a mild decrease of renal function (2.8 ml/mn per year of creatinin clearance), correction of hypokalemia above 3 mEq/l in 73% of patient with treatment, and mild elevation of blood pressure.

Conclusion: In adult patients referred for hypokalemia, GS should be evoked especially in case of hyperreninism that is a constant feature in patients with a confirmed genetic diagnosis. High blood pressure does not set the diagnosis aside. Mild hypokalemia are sometimes associated with heterozygous mutation of the SLC12A3 gene.