Clinical Characteristic And Genetic Analysis Of Gitelman Syndrome

Objective:To analyze the clinical characteristics and complications of Gitelman syndrome（GS）and the phenotypic characteristics among different gene types in order to deepen physicians’understanding and differential diagnosis of GS as well as reduce misdiagnosis and missed diagnosis.Methods:Clinical and laboratory findings of patients with a clinical diagnosis of BS/GS,who first treated in Tianjin Medical University General Hospital from Aug.2014 to Oct.2019,were retrospectively obtained from their medical records.Then patients with SLC12A3 mutations were enrolled and analyzed their characteristic of clinic,biochemistry and gene.Results:1、General conditions and symptoms.:Of the 12 patients diagnosed with GS,the mean age at first evaluation was 31.2±17.1 years（range:4-61）and the course of the disease was 2.9±2.5 years.The patients comprised 83.3%（10/12）males and 16.7%（2/12）females and men were significantly higher than women.Common clinical manifestations of GS consist of weakness（7/12）,numbness of limb（3/12）,oppression in chest（2/12）and palpitation（2/12）.Moreover,two case（16.7%）presented with hyperthyroidism and one case（8.3%）with undergrowth.Meanwhile,in our study,we found the longer the course,the more symptoms involved.2、Laboratory findings:All patients had hypokalemia（2.70±0.36 mmol/liter） associated with renal K⁺wasting（94.98±38.11mmol/24h）.Serum Mg2+and Urinary calcium were 0.67±0.23mmol/l and 0.69±0.71mmol/24h respectively.However,hypomagnesemia was not found in six（50%）patients and hypocalciurianot in one（8.3%）.Five patients with doing OGTT all had insulin resistance and four patients was diagnosed as abnormal glucose metabolism among3、Genotype analysis:Of the 15 patients with SLC12A3 gene mutation,18 different mutations were identified with 4 being novel（c.2951+2T>G,c.2874C>G,c.510del G,c.412G>A）.53.3%（8/15）patients had compound heterozygotes mutation,26.7%（4/15）homozygous mutation,20%（3/15）only one heterozygous mutation.And pathogenic mutations in SLC12A3 consisted of frameshift mutations（n=2）,splice site mutation（n=2）,missense mutation（n=14）.The most common genetic alterations of SLC12A3 was c.1456G>A（p.（Asp486Asn））（21.7%）.Meanwhile,there existed no significant difference among the three groups（homozygous mutation group,the compound heterozygous group,and multiple mutation group）in serum potassium and magnesium level and 24-h urine calcium excretion.4、Treatment:After treatment,serum potassium concentration in all patients was improved（from 2.60±0.34mmol/l to 3.26±0.3gmmol/l）,but hypomagnesemia not.Conclusion:1、In our study,we found the longer the course of GS,the more symptoms involved.2、Serum Mg²⁺cannot be alone used to distinguish GS from BS.3、Since GS patients are prone to abnormal glucose metabolism,they should be routinely OGTT examined.4、18 different SLC12A3 mutations were identified,of which c.1456G>A(p.（Asp486Asn）was the most common mutation site.4 novel were found（c.2951+2T>G,c.2874C>G,c.510del G,c.412G>A）,which had enriched the disease mutation database.5、Although there are still known mutations of disease-related genes that have not been found,and the limitations of gene detection itself,gene detection is still the gold standard for GS diagnosis.6、Hypomagnesemia and hypokalemia in GS patients could not be entirely corrected.