Gitelman Syndrome: Report Of 9 Cases And Literature Review

Objective: To provide more theoretical basis and experiences for clinical diagnosis and treatments of Gitelman Syndrome(GS),through summarying the clinical manifestations,urine protein and other laboratory tests,genetic tests,diagnosis and treatments of 9 patients with this disease and literature review.Methods: The clinical data of 9 patients with GS were retrospectively analyzed,including the biological characteristics,onset ages,urine protein and other laboratory examinations,diagnosis and treatments,and revelant domestic and foreign literatures were reviewed.Results: The onset ages of the 9 patients with GS were 2 to 46 years old,6 of them were male,and the other 3 were women.It is mainly manifested with limbs weakness,tetany,8 of 9 patients had different degrees of weakness of both lower limbs or malaise,1 case got lower limbs palsy,tetany were found in 3 cases,extremities numbness in 2 cases,4 cases got nausea and vomiting,dizziness and headache in 2cases,nocturia in 2 cases,heart palpitations in 1 case,1 case had abdominal distension and lossing appetite;The 9 patients had no history of laxative and thiazide diuretic abuse,no history of hypertension,no family history of dominant kidney disease,and no family history of hypokalemia,and all had normal blood pressure.With regard to laboratory tests,all the patients had different degrees of hypokalemia associated with increasing potassium excretion in the kidney,metabolic alkalosis,low urinary calcium and enhanced Renin Angiotensin Aldosterone System(RAAS,Renin-Angiotensin-Aldosterone System)activity(9/9),low blood magnesium in 8 cases(8/9),renal loss of chlorine in 6 cases(6/9).4 cases of these patients got different degree of proteinuria.Urine protein quantification was 663 mg /24 h in case 4,231.67mg/24 h in case 5,264mg/24 h in case 6,169mg/24 h in case 8,respectively.All the 4 patients with complicated with exact proteinuria have a long history,with a course of 10 to 34 years.It is speculated that proteinuria may occur due to kidney damage caused by long-term low potassium and high activity of RAAS.Case2 developed rhabdomyolysis due to severe hypokalemia;Case 2 was complicated with Graves Disease(GD),case 6 was complicated with type 2 diabetes,case 5 was complicated with psoriasis,and case 7 was complicated with pregnancy.Three of the patients were tested for SLC12A3 gene.Case 4 was found with SLC12A3 exon mutation in the Ruijin Hospital affiliated to Shanghai Jiao Tong University and his mother was also confirmed to be a carrier of this SLC12A3 gene mutation,since their original report was not provided,the mutation site was unknown.The results of gene detection in case 6 showed that the 179 th base of exon 1 in the third band of the long arm region of chromosome 16 was mutated from cytosine to thymine,which resulted in the 60 th amino acid of the encoded protein being changed from threonine to methionine.This mutation site is one of the most common pathogenic mutation sites in China.Two heterozygous SLC12A3 gene mutations were detected in case 9,both of which were located in zone 1 and zone 3 of the long arm of chromosome16.one mutation at the 1567 th base of exon 12 changed from guanine to adenine,resulting in the 523 th amino acid change from alanine to threonine,the other mutation at exon 15,the 1909 th base change from cytosine to thymine,resulting in the 637 th amino acid change from histidine to tyrosine.In the aspect of the imaging examination of the urinary system,all the 9 patients received urological ultrasound,case 6 and cases 8 showed kidney calculi by the urinary system ultrasound(which case 6 had been diagnosed by the genetic test),and the rest patients had no obvious abnormality in the urological examinations.In terms of the treatment,9 patients were treated with potassium supplementation alone or combined with potassium magnesium aspartate and spironolactone,and their symptoms were relieved,but blood potassium did not rise to normal level.Among those with hypomagnesemia,only case 7’s blood magnesium rose to the lower limit of normal value(0.7mmol/L),case 4 stopped taking spironolactone because of the side effect of male breast development.In case 2,the serum potassium decreased dramatically after 2days of withdrawal of spironolactone on the basis of continuous potassium and magnesium supplementation,and the serum potassium increased after resuming spironolactone oral administration.Patients with other diseases were treated accordingly,and their conditions improved.Conclusions:1.Excluding the evidence that does not support GS,GS should be considered for those patients with normal blood pressure,hypokalemia combined with increased renal potassium excreting,metabolic alkalosis,hypomagnesemia or normal serum magnesium,low urinary calcium,and SLC12A3 gene test should be performed for accurate diagnosis.2.It is not uncommon for GS patients to have proteinuria,proteinuria may not be related to SLC12A3 gene mutation site,but may be related to chronic hypokalemia,long-term high activity of RAAS.Kidney stones cannot rule out the diagnosis of GS.