Introduction. Simon et al (Nat Genet 12:24,1996) and our Group(Am J Hum Genet 59:1019,1996) demonstrated that molecular variants of the Na-Cl thiazide-sensitive cotransporter gene (TSC) are responsible for Gitelman Disease (GD), a hereditary renotubular disorder characterized by hypokalemia, metabolic alkalosis, hypomagnesemia and hypocalciuria. Lower lymphocytic potassium levels were detected in GD patients compared to controls (Bettinelli et al Kidney Int 47:547,1995). Aim. To investigate the cause of reduced intralymphocytic potassium levels in GD, with particular regard to the primary defect in Na-Cl tubular reabsorption. Patients and Methods. We evaluated the most important serum and urinary electrolytes and intralymphocytic potassium in 10 children and adolescents (aged 6-18 years) with GD. All patients presented: hypokalemia, Ks 3.2 (SD 0.3 mmol/l); metabolic alkalosis, HC03 32(1.1 mmol/l); hypomagnesemia, Mgs 0.60 (0.09 mmol/l); hypocalciuria, molar urinary calcium/creatinine 0.050 (0.040). Fractional excretion (Fe) of Na and Cl were 1.0 (0.6%) and 1.8 (1.1%), respectively. Intralymphocytic free potassium concentration was measured with the K+-sensitive fluorescent dye PBFI using a spectrofluorimetric method; Kd was approximately 100 mM in the presence of sodium. Molecular variants of TSC gene were demonstrated in 6 patients.
Results. The mean intralymphocytic potassium content amounted to 300mM (range 63-790 mM). We observed a significant inverse correlation(p<0.05) between free potassium levels and: 1) urinary Na excretion, expressed both as molar Na/creatinine (r=0.64) and FeNa (r=0.67); 2) urinary Cl excretion also expressed as molar Cl/creatinine (r=0.73) and FeCl(r=0.76).
