title: Genetic heterogeneity in tubular hypomagnesemia-hypokalemia with hypocalcuria (Gitelman's syndrome).
abstract: 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.
authors.affiliation: Istituto Clinica Pediatrica II, Univesritá di Milano, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Bettinelli
authors.forename: M G
authors.initials: MG
authors.lastname: Bianchetti
authors.forename: P
authors.initials: P
authors.lastname: Borella
authors.forename: E
authors.initials: E
authors.lastname: Volpini
authors.forename: M G
authors.initials: MG
authors.lastname: Metta
authors.forename: E
authors.initials: E
authors.lastname: Basilico
authors.forename: A
authors.initials: A
authors.lastname: Selicorni
authors.forename: A
authors.initials: A
authors.lastname: Bargellini
authors.forename: M R
authors.initials: MR
authors.lastname: Grassi
mesh_terms: D000293:Adolescent; D000328:Adult; D001477:Bartter Syndrome / Q000235:genetics*; D002118:Calcium / Q000172:deficiency* / Q000652:urine; D002648:Child; D005260:Female; D014644:Genetic Variation; D006801:Humans; D007008:Hypokalemia / Q000235:genetics* / Q000378:metabolism*; D007684:Kidney Tubules / Q000503:physiopathology*; D008275:Magnesium Deficiency / Q000097:blood / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D013577:Syndrome
chemical_list: D002118:Calcium