目的

探讨儿童Gitelman综合征（GS）患儿的临床表现及遗传学特征。

方法

选择2012年1月至2024年5月在苏州大学附属儿童医院被诊断为GS的22例住院患儿（患儿1～22）为研究对象。采用回顾性研究方法，收集其临床特征，如临床表现、初诊入院时实验室及影像学检查结果，以及遗传学特征，如全外显子组测序（WES）结果与住院治疗情况。本研究经苏州大学附属儿童医院伦理委员会批准（审批文号：2024CS104）。

结果

本研究对22例GS患儿临床及遗传学特征分析如下。①男、女性各为12、10例，初诊时年龄为2岁8个月至15岁3个月。②临床表现：18.2%（4/22）患儿初诊时无症状，其余81.8%（18/22）患儿均有相应临床症状，其中乏力、抽搐及身材矮小是最常见症状，分别占比为22.7%（5/22），其次为手足麻木（13.6%，3/22），呕吐、腹泻（9.1%，2/22），烦渴（4.5%，1/22）及夜尿多（4.5%，1/22）。③初诊入院时辅助检查结果：所有患儿均存在低钾血症，血浆K⁺浓度为（2.37±0.14）mmol/L，以重度低钾血症最常见（54.6%，12/22）；86.4%（19/22）患儿血浆Mg²⁺浓度降低，血浆Mg²⁺浓度为（0.66±0.11）mmol/L；81.8%（18/22）患儿24 h尿钙浓度低。④基因检测结果：12 例患儿（患儿1～4、6、9、10、12、13、19～21）因家属原因未进行WES检测；10例（患儿5、7～8、11、14～18、22）不伴有低镁血症或代谢性碱中毒者进行WES检测结果显示，均存在SLC12A3 基因突变，其中患儿22的SLC12A3 基因第5号外显子发生c.650G＞A 与c.506-1G＞A 复合杂合突变，c.650G＞A 为既往未报道的新发突变位点，根据美国医学遗传学与基因组学学会制定的《遗传变异分类标准与指南》，将其判断为疑似致病性突变（PM1+PM3+PP3），SIFT、PolyPhen-2、和Mutation Taster生物信息学软件预测结果亦被判断为可能致病突变。⑤治疗及转归：对22例患儿采取补钾、补镁治疗后，出院时有症状患儿相应症状均消失，16例患儿（患儿1～3、6～8、10、11、13～14、16～21）血浆K⁺浓度恢复正常，其余6例患儿（患儿4～5、9、12、15、22）血浆K⁺浓度＞3 mmol/L；而22例患儿血浆Mg²⁺浓度均＞0.6 mmol/L。

结论

GS患儿临床特征不典型，最常见症状为乏力、抽搐及身材矮小，所有患儿均有低钾血症，对于偶然发现的乏力、抽搐、身材矮小合并低钾血症患儿，应考虑GS可能。GS患儿遗传学特征存在SLC12A3 基因突变，WES检测有助于该病的诊断，本研究发现的c.650G＞A 新突变位点丰富了SLC12A3 基因突变谱。

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.