葡萄糖转运体1缺陷综合征疾病特征、基因型分析及生酮饮食治疗的临床研究

Clinical study on the disease characteristics,genotype analysis and ketogenic diet therapy of glucose transporter tape 1 deficiency syndrome

目的 探讨葡萄糖转运体1缺陷综合征(glucose transporter type 1 deficiency syndrome,GLUT1-DS)的临床表型和基因型特点及生酮饮食治疗的疗效。方法 回顾性分析了我院2019年1月至2023年12月收治的8例GLUT1-DS患儿,对其临床表现、脑脊液、脑电图、影像学、遗传学检测、治疗与转归进行总结。结果 8例患者中,其中男5例,女3例。发病年龄为3个月至8岁,5例患儿以癫痫发作为首诊症状,2例以发作性运动障碍为首诊症状,1例以精神行为异常合并运动障碍为首诊症状。6例患儿存在不同程度的精神运动发育迟缓。所有患儿进行了脑脊液检查,脑脊液糖水平均有不同程度的降低,范围在1.6至2.3 mmol/L之间,脑脊液糖/血糖比值范围在0.28至0.48之间。3例患儿的脑电图提示背景活动偏慢,3例为正常儿童脑电图,2例有痫样放电。5例患儿磁共振示未见明显异常,其余3例有非特异改变。8例患儿均进行了遗传学检测,其中4例为错义变异,3例为移码变异,1例为外显子大片段缺失变异。患儿均接受了生酮饮食治疗,起始均采用经典KDT,比例为2:1,疗程在7至41个月之间不等,目前未有因生酮不良反应或不耐受放弃者。除1例患儿疗效不显著外,其余患儿在癫痫发作、运动障碍、认识水平均有不同程度改善。结论 GLUT1-DS的临床表现复杂多样。对于难治性癫痫发作、发育迟缓和复杂运动障碍的儿童,脑脊液检查或SLC2A1基因突变检测有助于GLUT1-DS的诊断。早期开始生酮饮食治疗可显著改善GLUT1-DS的症状和预后。

Objective To explore the clinical characteristics,gene mutation characteristics and therapeutic effect of ketogenic diet on glucose transporter 1 deficiency syndrome(GLUT1-DS).Methods A retrospective analysis was performed on 8 children with GLUT1-DS admitted to our hospital from January 2019 to December 2023,and the detailed clinical manifestations of these 8 cases were recorded.Results Among the 8 cases,5 were males and 3 females.The age of onset ranged from 3 months to 96 months.Epilepsy was the first onset symptom of 8 cases.Paroxysmal dyskinesia was the first onset symptom of 2 cases.Psychobehavioral abnormalities combined with movement disorders was the first onset symptom of 1 case.6 cases had different degrees of psychomotor retardation.CSF examination was performed in all patients,and CSF sugar in all 8 cases was reduced to varying degrees,ranging from 1.6-2.3mmol/L,and CSF sugar/glucose ratio ranged from 0.28 to 0.48.3 cases showed slow background activity;3 cases were normal EEG;Epileptiform discharge occurred in 2 cases.5 cases were normal MRI and other cases had nonspecific changes.Genetic tests were performed in all 8 cases,among which 4 cases were missense variation,3 were frameshift variation and 1 was exon large fragment deletion mutation.All the children were treated with ketogenic diet,starting with classic KDT(2:1),the course of treatment ranged from 7 months to 41 months,and no one gave up due to ketogenic adverse reactions or intolerance.With the exception of 1 case,others had different degrees of improvement in seizure control,dyskinesia and cognitive function.Conclusion The clinical manifestations of glucose transporter type 1 deficiency syndrome are varied.For patients with refractory seizure,developmental retardation and complex dyskinesia,CSF examination or SLC2A1 gene mutation testing can help in the diagnosis of GLUT1-DS.Early initiation of ketogenic diet therapy may improve the symptom and prognosis of the patients.