11例原发性肾性糖尿患儿SLC5A2基因变异分析

Analysis of SLC5A2 gene variation in 11 children with primary renal glucosuria

目的总结原发性肾性糖尿(PRG)患儿的临床特点,分析SLC5A2基因变异情况。方法回顾性分析2013—2021年诊断PRG患儿的临床资料及基因检测结果。结果11例PRG患儿,男5例、女6例,男/女比例为1:1.2;诊断中位数年龄为29个月(1天~13岁);5例有糖尿家族史,均无糖尿病家族史;2例为轻度糖尿,9例为重度糖尿,所有患儿监测血糖、糖化血红蛋白、胰岛素、C肽、肾功能、肾脏超声均正常。患儿随访期间临床均无糖尿病“三多一少”症状或全身乏力表现,生长发育正常,无严重并发症。SLC5A2基因检测结果未发现纯合变异,杂合变异比例36%(4/11例),复合杂合变异64%(7/11例);共发现14种变异,其中有10种错义变异、1种缺失变异、3种剪接变异,其中5种变异文献已报道,p.S161F、p.A169T、p.P275L、p.A312P、p.A365T、p.Y410C、p.F471L、c.1889_1891del、c.1665+5G>C 9种变异为新发变异,软件及功能预测均可能致病。4例杂合变异患儿中,2例为轻度糖尿,2例为重度糖尿;7例复合杂合变异患儿均表现为重度糖尿。结论SLC5A2基因检测有助于PRG的诊断,其临床表型与基因型有一定的相关性,杂合变异可表现为轻度或重度糖尿,复合杂合变异多表现为重度糖尿,PRG多为良性过程,不影响儿童的生长发育。

Objective To summarize the clinical characteristics of children with primary renal glucosuria(PRG),and analyze the variation of SLC5A2 gene.Methods The clinical data and genetic test results of children diagnosed with PRG from 2013 to 2021 were retrospectively analyzed.Results There were 11 children(5 boys and 6 girls)with PRG,with a male/female ratio of 1:1.2.The median age at diagnosis was 29 months(1 day to 13 years).Five patients had a family history of glucosuria and none had a family history of diabetes.Two patients had mild and 9 patients had severe glucosuria.The blood glucose,glycated hemoglobin,insulin,C-peptide,renal function and renal ultrasound results were normal in all children.During the follow-up period,there were no symptoms of diabetes or systemic fatigue,and the children had normal growth and development without serious complications.No homozygous variation was found in SLC5A2 gene,the proportion of heterozygous variation was 36%(4/11),and the proportion of compound heterozygous variation was 64%(7/11).A total of 14 variants were found,including 10 missense variants,1 deletion variant and 3 splicing variants.Among them,5 variants have been reported in the literature,and 9 variants,p.S161F,p.A169T,p.P275L,p.A312P,p.A365T,p.Y410C,p.F471L,c.1889_1891del,and c.1665+5G>C,are new variants,which are predicted to be pathogenic by software and function.Among the 4 children with heterozygous variation,2 had mild and 2 had severe glucosuria.Seven children with compound heterozygous variation showed severe diabetes.Conclusions SLC5A2 gene detection is helpful for the diagnosis of PRG.The clinical phenotype of PRG is correlated with its genotype.Heterozygous variation may show mild or severe glucosuria,while compound heterozygous variation mostly shows severe glucosuria.The clinical manifestation of children with PRG is mostly benign and does not affect the growth and development of children.