Clinical severity of Gitelman syndrome determined by serum magnesium

Am J Nephrol. 2014;39(4):357-66. doi: 10.1159/000360773. Epub 2014 Apr 23.


Background/aims: Normomagnesemia is considered atypical in Gitelman syndrome (GS). Here, we describe clinical, pathological and genetic characteristics in Chinese GS patients with or without hypomagnesemia in order to determine whether serum magnesium concentration indicates the severity of the disease.

Methods: 7 normomagnesemic and 25 hypomagnesemic GS patients who were confirmed by direct sequencing of SLC12A3 gene were included. Clinical manifestation and laboratory tests were documented. Supine and upright plasma renin activity, angiotensin II and aldosterone were determined by radioimmunoassay. Transient receptor potential channel melastatin subtype 6 (TRPM6) was detected by immunohistochemistry in paraffin-embedded renal biopsy sections of 12 GS patients. 14 patients with glomerular minor lesion served as controls. The distribution of the mutations on the predicted NCC protein was analyzed and compared between two subgroups.

Results: Clinical manifestations, electrolyte abnormalities, metabolic alkalosis and renin-angiotensin-aldosterone system activation were found to be milder in normomagnesemic compared with the hypomagnesemic group. Compared with glomerular minor lesion controls, the TRPM6-positive area was significantly decreased in hypomagnesemic patients (4.96 ± 1.88 vs. 8.63 ± 2.67%) while it was near normal (7.82 ± 5.23%) in 2 normomagnesemic GS patients. A higher percentage of intracellular mutations was observed in normomagnesemic patients than hypomagnesemic patients (92.31 vs. 56.52%, p = 0.02).

Conclusions: Normomagnesemia is not rare in GS. Serum magnesium may indicate the severity of GS.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers / blood
  • DNA Mutational Analysis
  • Female
  • Gitelman Syndrome / blood*
  • Gitelman Syndrome / genetics
  • Humans
  • Kidney / metabolism
  • Magnesium / blood*
  • Male
  • Middle Aged
  • Renin-Angiotensin System
  • Severity of Illness Index
  • Solute Carrier Family 12, Member 3 / genetics
  • TRPM Cation Channels / metabolism
  • Young Adult


  • Biomarkers
  • SLC12A3 protein, human
  • Solute Carrier Family 12, Member 3
  • TRPM Cation Channels
  • TRPM6 protein, human
  • Magnesium