Analysis Of Clinical And Gene Mutation Characteristics Of Gitelman Syndrome

Objective:To analyze the clinical and gene mutation characteristics of patients with Gitelman syndrome.Methods:From 2009 to 2021,4494 inpatients diagnosed with hypokalemia were collected from the People’s Hospital of Xinjiang Uygur Autonomous Region.Among them,126 cases of unexplained hypokalemia were screened out.After completing the examination,24 cases of Gitelman syndrome were finally screened out.The clinical characteristics of the patients were described and matched with a healthy group of 48 cases and a control group of 48 cases according to age and gender.The differences in biochemical indicators between the case group,the healthy group,and the control group were compared,The genetic characteristics of 10 gene-diagnosed patients were analyzed.The improvement of symptoms and ion changes of the followed-up patients were also recorded.Results:①A total of 4494 inpatients with hypokalemia were collected,among whom 126 cases(2.8%)had unexplained hypokalemia,and 24 cases(19%)of Gitelman syndrome were screened out from the patients with unexplained hypokalemia.②Among the 24 patients with Gitelman syndrome,10 were female(41.67%)and 14 were male(58.33%).The average age of onset was(30.92±15.40)years,and the average age of diagnosis was(33.92±15.50)years.The BMI was(21.32±4.05)kg/m2 and the blood pressure was normal or low,with an average blood pressure of(112.88±15.25)mmHg/(72.54±12.54)mmHg(SBP/DBP,1 mmHg=0.133 kPa).The average course of the disease was(3.00±4.25)years.Among the clinical symptoms of GS patients,limb weakness was the most common clinical symptom(37.50%),followed by asymptomatic symptoms(20.83%),etc.The blood potassium level was(2.83±0.33)mmol/L,the urine potassium level was(69.98±27.01)mmol/24h,the blood magnesium level was(0.60±0.16)mmol/L,the urine magnesium level was(4.03±2.00)mmol/24h,and the urine calcium level of the patients was(2.372±12.636)mmol/24h.③The clinical characteristics of 24 cases in the case group,48 cases in the control group,and 48 cases in the healthy group were compared and analyzed.The proportion of patients with combined diabetes and thyroid disease in the case group was significantly higher,and there were statistical differences in uric acid,alanine aminotransferase,aspartate amnotransferase,albumin,erythrocyte sedimentation rate,C-reactive protein,triglycerides,total cholesterol,blood potassium,and blood calcium among the three groups.④The clinical characteristics of GS patients of different genders were compared,and there were differences in total cholesterol,osteocalcin,hemoglobin,and alkaline phosphatase levels between males and females.⑤The GS patients were divided into severe hypokalemia group(4 cases),moderate hypokalemia group(13 cases),and mild hypokalemia group(7 cases)according to the severity of hypokalemia,and there were differences in systolic and diastolic blood pressure among the three groups.There were also statistical differences in blood potassium,blood urea nitrogen,and thyroid-stimulating hormone among the three groups.⑥The average course of the disease in GS patients was(3.00±4.25)years.According to the length of the course of the disease,GS patients were divided into two groups with a boundary of 3 years.There were statistical differences in fasting blood glucose and serum uric acid between the two groups.⑦Ten patients completed genetic testing,all of whom had SLC12A3 gene mutations.A total of 13 mutation sites were found in the SLC12A3 gene,including 2 homozygous mutations,4 heterozygous mutations,and 4 compound heterozygous mutations.Three new mutation sites were discovered,namely V64E,T163P,and N566K.The pathogenicity of the three new sites was predicted using Mutation Taster software,and all three new sites were pathogenic.There were clinical differences in the course of the disease and urine magnesium between different mutation types of GS patients⑧During the follow-up of 24 patients with an interval of at least 1 year,4 patients did not take oral medication after discharge,and the remaining 20 patients took oral potassium supplements.The blood potassium concentration was(2.83±0.33)mmol/L at admission and(3.13±0.54)mmol/L at follow-up,and there were statistical differences before and after treatment(t=-2.411,P=0.024).The blood magnesium concentration was(1.00±0.21)mmol/L and(1.21±0.30)mmol/L before and after treatment,respectively,and there were statistical differences before and after treatment(t=-3.545,P=0.002).There was a significant positive correlation between potassium ion and magnesium ion after treatment(Pearson=0.551,P=0.001).The symptoms of 16 patients were currently asymptomatic,7 patients still had fatigue but improved compared to before,and 1 patient had aggravated fatigue.Conclusion:①In this study,the proportion of Gitelman syndrome in unexplained hypokalemia was higher,reaching 19%,and Gitelman syndrome should be actively screened in unexplained hypokalemia.②In this study,Gitelman syndrome was more likely to be combined with diabetes,thyroid disease,and manifested as higher levels of alanine aminotransferase,aspartate aminotransferase,C-reactive protein,triglycerides,erythrocyte sedimentation rate,albumin,and total cholesterol.③In GS patients,the lower the blood potassium level,the lower the diastolic and systolic blood pressure.The longer the course of the disease,the higher the fasting blood glucose and uric acid levels.Gitelman syndrome should be identified and screened early for potassium supplementation to prevent further reduction of blood potassium and magnesium.④The genetic characteristics of Gitelman syndrome are that the pure and mutant groups have a longer course of disease and higher urine magnesium levels than the heterozygous mutant group.In addition,this study found three new loci in 10 GS patients with complete genetic testing,namely V64E,T163P,and N566K,which enriched the genetic loci of Gitelman syndrome mutations.