GENETIC-HETEROGENEITY IN TUBULAR HYPOMAGNESEMIA HYPOKALEMIA WITH HYPOCALCURIA (GITELMANS SYNDROME)

To better clarify the genetic inheritance of primary tubular hypomagne semia-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, wh o all had tetanic episodes and/or marked weakness during childhood or adolescence, whereas in three other families two mothers and three off spring presented GS and one father and two other offspring had hypomag nesemia and hypocalciuria but normal plasma potassium. The mean plasma magnesium and potassium levels of the patients of the first two famil ies were significantly lower (P < 0.05) than those of the other three families. Intralymphocytic but not intraerythrocytic magnesium and pot assium were significantly lower (P < 0.05) in patients compared to con trols. We hypothesize that there are two different types of genetic tr ansmission of GS, one autosomal recessive and one autosomal dominant w ith high phenotypic variability. It seems that this genetic heterogene ity is associated with a different clinical expression with frequent t etanic episodes and lower plasma potassium and magnesium levels in the autosomal recessive form.