探讨Gitelman综合征(GS)患儿的临床特征及基因变异情况。

选择2024年11月30日于西安市儿童医院确诊的1例GS患儿(患儿1)为研究对象。采用回顾性分析方法，收集患儿1的临床资料、全外显子组测序(WES)及Sanger测序验证结果。根据美国医学遗传学基因组学学会(ACMG)制定的《遗传变异分类标准与指南》(以下简称为"ACMG指南")，对检出的基因变异位点进行致病性评级。以"Gitelman综合征""Gitelman syndrome""SLC12A3"为中、英文关键词，在中国知网、万方数据库、维普中文科技期刊数据库及PubMed数据库中检索被明确诊断为SLC12A3基因突变所致GS患儿研究的相关文献。本次文献检索时间设定为2022年1月1日至2025年3月31日。本研究遵循的程序符合西安市儿童医院伦理委员会规定，通过该伦理委员会审查(伦理审批号：20240133)，并征得患儿1监护人的知情同意。

①患儿1为男孩，6岁6个月，以"间断呕吐14 d"收入病例收集医院儿童肾病科治疗。入院实验室检查结果提示，血清K^＋浓度为1.64 mmol/L(偏低)，血清Cl^－浓度为89.7 mmol/L(偏低)，血清Mg^2＋、Ca^2＋和Na^＋浓度均正常。患儿1经多次补钾治疗后效果不佳，低钾血症病因不明，考虑遗传性疾病可能。WES结果显示，患儿1 SLC12A3基因存在c.1956delC(p.Asn653Thrfs*19)与c.2029G>A(p.Val677Met)复合杂合突变，可能遗传自父母。根据患儿1临床表现与基因检测结果，患儿1被确诊为GS。对其采取口服氯化钾缓释片及螺内酯治疗后，随访至2025年5月31日，患儿1未再出现反复呕吐症状，血清电解质维持在正常水平。②文献复习结果：根据本研究设定的文献检索策略，检索到国内外关于SLC12A3基因突变所致GS患儿研究的文献为20篇，纳入GS患儿为24例，7例伴生长缓慢，3例起病时主要临床表现为呕吐症状。24例患儿均表现为低钾血症，6例患儿血清Mg^2＋浓度正常，其余患儿有不同程度的低氯性碱中毒、低磷血症、低尿钙症及肾素-血管紧张素-醛固酮(RAAS)水平升高。

儿童期GS患儿常缺乏特异性临床表现，对于难以纠正的低钾血症和代谢性碱中毒，应高度怀疑GS可能。早期对GS患儿进行基因检测，有助于明确诊断并对其早期治疗。

To investigate the clinical characteristics and genetic variations of Gitelman syndrome (GS).

A case of GS diagnosed in November 2024 at Xi′an Children′s Hospital (patient 1) was included in the study. Clinical data, whole-exome sequencing (WES) results, and sanger sequencing validation results of patient 1 were retrospectively collected. Variants identified were classified for pathogenicity according to the Standards and Guidelines for the Interpretation of Sequence Variants by the American College of Medical Genetics and Genomics (ACMG). Literature on pediatric GS cases confirmed to be caused by SLC12A3 gene mutations was retrieved from the China National Knowledge Infrastructure (CNKI), Wanfang Database, VIP Chinese Science and Technology Journal Database, and PubMed, using the Chinese and English keywords " Gitelman syndrome" and " SLC12A3". The literature search period was set from January 1, 2022, to March 31, 2025. The procedures of this study complied with the regulations of the Ethics Committee of Xi′an Children′s Hospital and were approved by the committee (Approval No.20240133). Informed consent was obtained from the guardian of patient 1.

①The patient is a 6-year-and-6-month-old boy who admitted to case collected hospital with " intermittent vomiting for two week." The results of relevant auxiliary examinations at admission showed low serum K⁺ concentration which was 1.64 mmol/L and low serum Cl^- concentration which was 89.7 mmol/L while serum Mg²⁺, Ca²⁺, and Na⁺ concentrations were normal. Despite repeated potassium supplementation, the therapeutic response was poor. The etiology of hypokalemia remained unclear, suggesting the possibility of an underlying genetic disorder. His result of genetic testing showed SLC12A3 gene compound heterozygous mutations: c. 1956delC(p.Asn653Thrfs*19) and c. 2029G>A(p.Val677Met), inherited from his father and mother, respectively. Based on his clinical manifestations and genetic testing results, he was diagnosed as GS. After oral treatment by potassium chloride and spironolactone, the patient 1 showed no recurrence of vomiting symptoms upon follow-up until May 2025, with serum electrolyte levels remaining within normal ranges. ②Literature review results: a total of 20 pieces of relevant research literature involving 24 cases of GS children caused by SLC12A3 gene mutations were retrieved. Among them, 7 cases exhibited growth retardation, and 3 cases primarily presented with vomiting symptoms at onset. All patients demonstrated hypokalemia. Six cases showed normal serum magnesium levels, while the remaining patients exhibited varying degrees of hypochloremic alkalosis, hypophosphatemia, hypocalciuria, and elevated renin-angiotensin-aldosterone system activity.

Childhood GS has an atypical clinical presentation in childhood. The presence of refractory hypokalemia and metabolic alkalosis warrants high clinical suspicion, and prompt genetic confirmation is critical for diagnosis and treatment.