Objective

To explore the clinical features and genetic characteristics of children with Gitelman syndrome（GS）.

Methods

Twenty-two hospitalized children （children 1 to 22）who were clinically diagnosed with GS from January 2012 to May 2024 at Children's Hospital of Soochow University were selected in the study.Retrospective study method was used to collect the clinical features，including clinical presentation，laboratory and imaging findings at the time of initial admission，and genetic characteristics such as whole exome sequencing（WES）results and treatment of the 22 children with GS.The study was approved by the Ethics Committee of Children's Hospital of Soochow University （Approval No.2024CS104）.

Results

The clinical and genetic characteristics of the 22 children with GS were as follows.①There were 12 males and 10 females，with an initial diagnosis age ranging from 2 years and 8 months to 15 years and 3 months.②Clinical manifestations：18.2%（4/22）of them were asymptomatic at the time of initial diagnosis，and the remaining 81.8%（18/22）of them had corresponding clinical symptoms，of which malaise，convulsions，and short stature were the most common ones，accounting for 22.7%（5/22）each，followed by n umbness of the hands and feet （13.6%，3/22），vomiting and diarrhea （9.1%，2/22），polydipsia （4.5%，1/22）and nocturnal polyuria （4.5%，1/22）.③Auxiliary examination results at initial diagnosis：all children had hypokalemia，and the plasma potassium concentration was （2.37±0.14）mmol/L，severe hypokalemia was the most common （54.6%，12/22）.And 86.4%（19/22）of the children had reduced plasma magnesium concentration，and the plasma magnesium concentration was （0.66±0.11）mmol/L；and 81.8%（18/22）of the children had decreased 24-hour urinary calcium.④Genetic testing results：12 children （children 1-4，6，9，10，12，13，19-21）did not receive WES due to family-related reasons，and the other 10 children （children 5，7-8，11，14-18，22）who did not have hypomagnesemia or metabolic alkalosis underwent WES testing，and all these 10 cases revealed mutations in the SLC12A3 gene.Children 22 had c.650G ＞A and c.506-1G ＞A compound heterozygous mutations in exon 5 of the SLC12A3 gene.The c.650G＞A mutation was a novel mutation site which had not been reported before，and was judged to be likely pathogenic variant（PM1+PM3+PP3）according to the StandardsandGuidelinesfortheInterpretationofSequence Variants by A merican College of Medical Genetics and Genomics （ACMG）.Bioinformatics predictions by SIFT，PolyPhen-2，and Mutation Taster also indicated likely pathogenic.⑤Treatment and outcomes：all 22 children were treated with potassium and magnesium supplementation during hospitalization，and the corresponding symptoms of symptomatic children disappeared at the time of discharge，16 children （children 1-3，6-8，10，11，13-14，16-21）had normal plasma potassium concentrations，and the remaining 6 cases （children 4-5，9，12，15，22）had plasma potassium concentrations＞3 mmol/L，and blood magnesium of all the 22 children were＞0.6 mmol/L.

Conclusions

The clinical symptoms of children with GS were atypical，and the most common symptoms are malaise，convulsions，and short stature.All the patients have hypokalemia，GS should be considered as an option for children with incidental hypokalemia，short stature，and convulsions combined with hypokalemia.There are mutations in SLC12A3 gene in children with GS.WES is helpful for the diagnosis of GS and the discovery of novel mutation site c.650G＞A enriches the variation spectrum of SLC12A3 gene variants.