Chinese Medical E-ournals Database

Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition) ›› 2020, Vol. 16 ›› Issue (06): 695 -701. doi: 10.3877/cma.j.issn.1673-5250.2020.06.011

Special Issue:

Original Article

Analysis of diagnosis and treatment of children with glucose transporter 1 deficiency syndrome and literature review

Guiyun Yang1, Xianyu Hou1, Maoqiang Tian2, Ying Yuan1, Fuxing Li3,()   

  1. 1. Department of Pediatrics, Chishui People′s Hospital, Zunyi 564700, Guizhou Province, China
    2. Department of Pediatrics, Affiliated Hospital of Zunyi Medical University, Zunyi 563000, Guizhou Province, China
    3. Department of Pediatrics, Tongji Hospital of Tongji University, Shanghai 200065, China
  • Received:2020-01-17 Revised:2020-11-13 Published:2020-12-01
  • Corresponding author: Fuxing Li
  • Supported by:
    National Natural Science Foundation of China(81760309)
Objective

To investigate clinical features of Chinese children with glucose transporter 1 deficiency syndrome (GLUT1-DS).

Methods

By retrospectively analytic method, clinical data of a girl with GLUTl-DS who was diagnosed and treated in Chishui People′s Hospital in June 2018 was selected. The clinical manifestation, diagnosis, treatment measures and sequelae of GLUT1-DS of domestic population were summarized by reviewing Chinese and English literature of GLUT1-DS with basically complete clinical data in domestic and foreign databases. This study was approved by the Ethics Committee of Cishui People′s Hospital (Approval No. 201801). Informed consent was obtained from the guardian of this child for the diagnosis and treatment.

Results

① The girl was diagnosed with GLUTl-DS at 2 years and 4 months old as main clinical manifestations of paroxysmal facial cyanosis, microcephaly, developmental retardation and dyskinesia. Monitoring results of video EEG was abnormal, levels of cerebrospinal fluid glucose, and levels of cerebrospinal fluid glucose to levels of plasma glucose ratio (cerebrospinal fluid glucose/plasma glucose) were both decreased. Gene detection (Sanger method) showed heterozygous missense mutation of exon 5: C. 661G>A (p.E221K) (from her father). The girl was intolerant to ketogenic diet (KD) therapy and response poorly to 6 months of Traditional Chinese Medicine rehabilitation treatment in other hospital. After followed up to 3 years and 11 months old, motor and language development of the girl was obviously behind that of normal children. ② Results of literature review: the clinical data of 18 cases with GLUTl-DS in China including 17 cases from 7 pieces of Chinese or English literature and one case in this study were summarized as follows. The male to female ratio of GLUTl-DS incidence was 10∶8, the median age of onset was 7 months, and the median age at diagnosis was 55 months. Main clinical symptoms were epileptic seizures (94.4%, 17/18), development retardation (88.9%, 16/18) and ataxia (72.2%, 13/18). The cerebrospinal fluid glucose concentration, and cerebrospinal fluid glucose/plasma glucose decreased in all the 18 cases (100.0%). SLC2A1 gene screening were performed in 17 cases, and revealed gene mutation in 15 cases. KD therapy were administered in 11 cases, and symptoms were effectively controlled in 8 cases but another 3 cases discontinued KD therapy due to intolerance. Four cases achieved good treatment results by increase the frequency of meals and high carbohydrate intake.

Conclusions

Typical clinical manifestations, laboratory examination and SLC2A1 gene detection results, can confirm the diagnosis of GLUTl-DS. For suspected or clinically diagnosed patients with GLUTl-DS, early start of KD therapy or increase the frequency of eating or sugar intake evidently can improve their prognosis.

图1 本例GLUT1-DS患儿(女性,2岁4个月龄)及其父母SLC2A1基因Sanger法测序图[红色箭头所示为患儿及其父亲均存在第5外显子C.661G>A(p.E221K)杂合错义突变,患儿母亲该位点无突变]
表1 本例及文献纳入研究的17例GLUTl-DS患儿临床病例资料分析
病例(No.) 文献(第1作者,文献发表年) 发病年龄 诊断年龄 性别 痫性发作 智力、运动发育落后 共济失调 踝阵挛 语言障碍 小头畸形
1 刘燕燕[5],2013 41 d 3个月
2 刘燕燕[5],2013 60 d 3个月
3 刘燕燕[5],2013 33 d 6岁
4 刘燕燕[5],2013 3岁7个月 7岁
5 刘燕燕[5],2013 6岁2个月 6岁5个月
6 刘燕燕[5],2013 2岁10个月 5岁
7 李晓华[6],2014 6个月 6个月
8 李晓华[6],2014 73 d 4个月
9 余宾[7],2015 2个月 2岁6个月
10 叶小飞[8],2012 2个月 2个月
11 段丽芬[9],2016 9个月 6岁1个月
12 Fung[10],2010 18个月 5岁
13 Fung[10],2010 8个月 17岁
14 姬辛娜[11],2018 11个月 4岁2个月
15 姬辛娜[11],2018 15个月 11岁1个月
16 姬辛娜[11],2018 2个月 3岁4个月
17 姬辛娜[11],2018 6个月 6岁
18 杨贵云,2020 1岁 2岁2个月
病例(No.) 其他症状 视频脑电图 头颅CT或MRI SLC2A1基因检测 脑脊液葡萄糖浓度(mmol/L) 脑脊液葡萄糖/血糖
1 多灶痫样放电 轻度脑萎缩 2号外显子大片段缺失 1.10~2.45,平均为1.68b 0.16~0.51,平均为0.34b
2 正常 正常 5号外显子C.741G>A(E247K)    
3 晨起及餐前发作性困倦、无力 正常 双侧脑室饱满 5号外显子C.599delA    
4 发作性无力、睡眠增多、意识障碍 正常 脑白质发育迟缓 6号外显子C.761delA    
5 发作性精神症状 慢波、全导和局灶痫样放电 正常 9号外显子C.1148C>A(P383H)    
6 发作性无力 正常 正常 9号外显子C.1198C>T(R400C)    
7 肌张力低下 背景为弥散性2~ 3 Hz低波幅δ波 未作 未发现基因突变点 1.60 0.24
8 左膝腱反射略活跃 双额及中央顶、枕区多灶性棘波、尖波、多棘波散发或簇发 未作 8号外显子C.972+1G>C 2.30 0.32
9 运动障碍 背景活动慢,以中高幅4~5 Hz θ波为主 正常 C.516 +2T>G(杂合突变)a 1.35 0.32
10 δ活动为主 正常 未描述 1.10 0.21
11 晨起头痛,空腹行走不稳 广泛性棘慢波发放 正常 4号外显子C.350_385del 1.87 0.36
12 肌张力障碍 正常 正常 2号外显子240delC 1.80 0.38
13 饥饿时发作性无力 正常 正常 8号外显子杂合突变c.1176 C>T(R333W) 1.90 0.38
14 空腹或玩耍时发作性肢体瘫痪、肌张力异常、震颤 全导阵发性高幅慢波,夹杂癫痫放电 正常 6号外显子c.787_791delTTCCG(p.F263Lfs) 均降低,但是未提供具体数据c 均降低,但是未提供具体数据c
15 肌张力异常,发作性眼球运动障碍 右侧大脑半球持续性慢波,右侧大脑半球及左侧额区癫痫放电 双侧额叶皮层下异常信号 4号外显子c.376G>A(p.R126C)    
16 震颤、肌张力异常,发作性眼球运动障碍 全导癫痫放电,以额区、枕区显著 双侧额、颞叶脑沟增宽 6号外显子c.377G>A(p.R126H)    
17 肌张力异常 双侧额、中央及额中线区偶见不典型尖波 正常 6号外显子c.688_689 insT    
18 肌张力升高 醒睡各期大量弥散性快波或快波节律发放,睡眠期多灶性棘波、尖波、棘慢波发放 正常 5号外显子c.661G>A 2.43 0.44
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