Magnesium supplementation in Gitelman syndrome.

The metabolism of potassium and magnesium are closely linked (in situations where potassium and magnesium depletion coexist, magnesium restoration alone is sufficient to correct hypokalemia). Moreover, magnesium deficiency blunts the interplay between circulating calcium and the calciotropic hormones. Renal magnesium wasting, hypokalemia, alkalosis, hypocalciuria, and a tendency towards hypocalcemia characterize Gitelman syndrome. Plasma or intracellular potassium, circulating calcium, and calciotropic hormones were therefore investigated in eight patients (4 females, 4 males, aged 9-20 years) with Gitelman syndrome before and during oral supplementation with magnesium pyrrolidone carboxylate 30 mmol daily for 4 weeks. Magnesium supplementation significantly increased plasma and intracellular magnesium and plasma calcium, but failed to completely restore magnesium deficiency. In contrast, blood levels of parathyroid hormone and calcitriol and plasma and intracellular potassium were not modified following magnesium administration.

Normal prostaglandinuria E2 in Gitelman's syndrome, the hypocalciuric variant of Bartter's syndrome.

In familial Bartter's syndrome, hyperprostaglandinuria is considered a constant feature and prostanoid synthetase inhibition often positively influences the disease course. The urinary calcium excretion distinguishes two clinically and biochemically different variants, namely, classic Bartter's syndrome (normocalciuric or hypercalciuric variant; urinary calcium to creatinine > or = 35.3 mg/mg 10(-3)) and Gitelman's syndrome (hypocalciuric variant; urinary calcium to creatinine < 35.3 mg/mg 10(-3)). In the hypocalciuric variant of Bartter's syndrome prostanoid synthetase inhibition is of little benefit. Since the production of prostanoids has not been extensively studied in Gitelman's syndrome, the urinary excretion of prostaglandin E2 was assessed by radioimmunoassay in 11 untreated patients with Gitelman's syndrome (aged 10 to 21 years; five females and six males) and in 11 healthy controls (aged 11 to 20 years; five females and six males). The urinary excretion of prostaglandin E2 was similar in both study groups. The study provides the rationale for the poor effect of prostanoid synthetase inhibition in the hypocalciuric variant of Bartter's syndrome. The assessment of urinary excretion of prostaglandin E2 does not represent a diagnostic sine qua non in the context of familial Bartter's syndrome.

Genetic heterogeneity in tubular hypomagnesemia-hypokalemia with hypocalcuria (Gitelman's syndrome).

To better clarify the genetic inheritance of primary tubular hypomagnesemia-hypokalemia with hypocalciuria, or Gitelman's syndrome (GS), we studied eight families (10 patients aged 11 to 22 years; 16 parents; 9 siblings) in which at least one offspring had GS (plasma magnesium < 0.65 mmol/liter; plasma potassium < 3.6 mmol/liter; high magnesium and potassium fractional excretions; molar urinary calcium/creatinine < 0.10). Two families each had two offspring of different sex with GS, who all had tetanic episodes and/or marked weakness during childhood or adolescence, whereas in three other families two mothers and three offspring presented GS and one father and two other offspring had hypomagnesemia and hypocalciuria but normal plasma potassium. The mean plasma magnesium and potassium levels of the patients of the first two families were significantly lower (P < 0.05) than those of the other three families. Intralymphocytic but not intraerythrocytic magnesium and potassium were significantly lower (P < 0.05) in patients compared to controls. We hypothesize that there are two different types of genetic transmission of GS, one autosomal recessive and one autosomal dominant with high phenotype variability. It seems that this genetic heterogeneity is associated with a different clinical expression with frequent tetanic episodes and lower plasma potassium and magnesium levels in the autosomal recessive form.

Evidence for disturbed regulation of calciotropic hormone metabolism in gitelman syndrome.

Little attention has been paid to interactions between circulating levels of calcium, PTH, and 1,25-dihydroxycholecalciferol [1,25(OH)2D] and bone mineral density in primary renal magnesium deficiency. Plasma and urinary electrolytes, and circulating levels of calciotropic hormones were studied in 13 untreated patients with primary renal tubular hypokalemic alkalosis with hypocalciuria and magnesium deficiency. The blood ionized calcium concentration was significantly lower in patients than in controls. Despite this fact, PTH and 1,25-(OH)2D levels were similar in both groups of subjects. The negative linear relationships between PTH and ionized calcium, which significantly differed between Gitelman patients and healthy subjects in terms of intercept; the negative relationship between ionized calcium and 1,25-(OH)2D, which was comparable in both groups; and the positive relationship between 1,25-(OH)2D and PTH, which was identical in both groups, point both to a blunted secretion of PTH induced by magnesium depletion and to the lack of interference of the latter with the activation of 1 alpha-hydroxylase by PTH. The similar bone mineral density at the lumbar spine by dual energy x-ray absorptiometry in 11 patients and 11 healthy subjects argues against chronically sustained negative calcium balance.

Renal tubular function in children and adolescents with Gitelman's syndrome, the hypocalciuric variant of Bartter's syndrome.

Renal tubular function was studied in 14 patients with Gitelman's syndrome and 14 control subjects. Apart from the biochemical hallmarks of Gitelman's syndrome, namely alkalaemia, hyperbicarbonataemia, hypokalaemia, hypomagnesaemia (with increased magnesium over creatinine ratio), increased urinary chloride over creatinine ratio, and low urinary calcium over creatinine, the patients were found to have hyperproteinaemia, hypochloraemia, high total plasma calcium concentration, reduced plasma ionized calcium concentration, and high urinary sodium excretion. A statistically significant negative linear relationship between plasma magnesium concentration and magnesium excretion corrected for glomerular filtration was observed in patients. The fractional calcium clearance and the urinary excretion of calcium corrected for glomerular filtration was significantly decreased in patients. In patients the urinary osmolality after overnight water deprivation ranged from 526 to 1067 mmol/kg. Glucosuria and aminoaciduria were similar in patients and controls. The results of the study demonstrate the renal origin of hypomagnesaemia and hypocalciuria in Gitelman's syndrome. The failure to demonstrate hyperaminoaciduria, hyperglucosuria, hyperphosphaturia, hyperuricosuria, and severely impaired urinary concentrating ability provide evidence for a defect residing in the distal convoluted tubule.

Long-term follow-up of a patient with Gitelman's syndrome.

The long-term follow-up (from age 6 to 20 years) of a girl with Gitelman's syndrome, who had four hypomagnesaemic-tetanic episodes associated with normal plasma calcium, hypokalemia and hypocalciuria, is presented. During and after puberty, hypomagnesaemia was of the order of 0.41-0.49 mmol/l and plasma potassium was at the lower reference limit. The long-term clinical course and growth of this patient appeared good, but, magnesium supplementation reduces the risk of tetanic crises.