儿童Gitelman综合征的临床特征、基因型及预后分析

Clinical features,genotypes,and prognosis of Gitelman syndrome in children

目的提高对Gitelman综合征(GS)患儿的临床特征、基因型及长期预后的认识。方法回顾性分析2015年1月至2019年12月在汕头大学附属深圳市儿童医院住院,临床诊断且基因确诊的13例(男6例、女7例)GS患儿的临床资料及基因信息,分析其临床及基因型特点,并对其进行平均4.5年的随访,了解其长期预后。采用χ2检验、秩和检验。结果在13例GS患儿中,发病年龄为(6.40±3.52)年,诊断年龄为(8.20±3.99)年;乏力是最主要临床表现,占54%(7/13),身材矮小占23%(3/13),8%(1/13)患儿无症状。所有患儿均检测出SLC12A3基因突变,1例(8%)纯合突变,9例(70%)复合杂合突变,3例(23%)只发现1个变异位点;其中R871H、T63M、T304M为重复氨基酸变异。平均随访4.5年,所有规范治疗患儿[69%(9/13)]临床症状消失,92%(12/13)患儿治疗后得到生长追赶。结论GS临床表现缺乏特异性,乏力为最常见的临床表现。详细的实验室检查结合基因检测可以及时诊断,规范管理可改善患儿的长期预后及生活质量。

Objective To improve the understanding of clinical features,genotypes,and long-term prognosis of children with Gitelman syndrome(GS).Methods The clinical characteristics and genotypes of 13 children with GS diagnosed in Shenzhen Children's Hospital Affiliated to Shantou University from January 2015 to December 2019 were retrospectively analyzed,including 6 boys and 7 girls.They were followed for an average of 4.5 years to understand their long-term prognosis.χ2 test and rank sum test were used.Results Among the 13 children with GS,the age of onset was(6.40±3.52)years old and the age of diagnosis was(8.20±3.99)years old.Fatigue was the most common clinical manifestation,accounting for 54%(7/13),short stature accounted for 23%(3/13),and 8%(1/13)were asymptomatic.Disease-causing variants in the SLC12A3 gene were found in all the 13 children,with homozygous mutation in 1 case(8%),compound heterozygous mutation in 9 cases(70%),and only 1 mutation site in 3 cases(23%).Among them,R871H,T63M,and T304M recurrently occurred.During an average follow-up of 4.5 years,all the children receiving standard treatment 69%(9/13)had no clinical symptoms,and 92%(12/13)had growth catch-up after treatment.Conclusions Fatigue is the most common clinical manifestation in children with GS.The clinical manifestation of GS lacks specificity.Detailed laboratory tests combined with genetic testing is beneficial to timely diagnosis,and standardized management can improve the long-term prognosis and quality of life in children.