CAJ | 학술논문

目的探讨葡萄糖转运子1缺乏综合征(GLUT1-DS)的临床与SLC2A1基因突变特点.方法对6例GLUT1-DS患儿的临床表现、脑脊液、脑电图、头颅影像学、治疗与转归等临床资料进行总结；应用聚合酶链式反应与测序、多重连接探针扩增技术对SLC2A1基因进行突变分析.结果本组6例,3例患儿为经典型GLUT1-DS,以早发惊厥为主要临床表现,3例患儿为非经典型GLUT1-DS,表现为发作性精神行为异常、意识障碍、共济失调等.5例患儿伴智力运动发育落后.6例患儿血糖均正常,脑脊液糖在1.10 ～2.45 mmoL/L之间,均降低,平均值1.68 mmol/L,脑脊液糖与血糖比值为0.16 ～0.51:1,均降低,平均值0.34.4例患儿脑电图正常,2例有局灶性或弥漫性(癎)样放电,其中一例同时有大量弥漫性慢波.3例头颅MRI正常,3例呈非特异性改变,其中1例呈轻度脑萎缩,1例双侧脑室饱满,1例左侧额、枕叶白质发育迟缓.6例患儿均存在SLC2A1基因突变,例1于第2外显子存在大片段缺失,例2至例6分别为c.741 G＞A(E247K)、599delA、761delA、c.1148 C＞A(P383H)、c.1198 C＞T(R400C).2例患儿行生酮饮食治疗,3例予增加饮食次数,疗效显著,1例放弃治疗.结论 GLUT1-DS临床症状多样,以癫(癎)及多种发作性的临床症状为主要表现,饥饿与疲劳可诱发临床症状的出现或加重,此特点为本病重要的临床诊断线索,而脑脊液糖与血糖比值的降低是本病最为重要的临床诊断依据.GLUT1-DS是可治性的神经系统疾病,早诊断、早治疗可显著改善患儿的预后.
목적 탐토포도당전운자1결핍종합정(GLUT1-DS)적림상여SLC2A1기인돌변특점.방법 대6례GLUT1-DS환인적림상표현、뇌척액、뇌전도、두로영상학、치료여전귀등림상자료진행총결；응용취합매련식반응여측서、다중련접탐침확증기술대SLC2A1기인진행돌변분석.결과 본조6례,3례환인위경전형GLUT1-DS,이조발량궐위주요림상표현,3례환인위비경전형GLUT1-DS,표현위발작성정신행위이상、의식장애、공제실조등.5례환인반지력운동발육락후.6례환인혈당균정상,뇌척액당재1.10 ～2.45 mmoL/L지간,균강저,평균치1.68 mmol/L,뇌척액당여혈당비치위0.16 ～0.51:1,균강저,평균치0.34.4례환인뇌전도정상,2례유국조성혹미만성(간)양방전,기중일례동시유대량미만성만파.3례두로MRI정상,3례정비특이성개변,기중1례정경도뇌위축,1례쌍측뇌실포만,1례좌측액、침협백질발육지완.6례환인균존재SLC2A1기인돌변,례1우제2외현자존재대편단결실,례2지례6분별위c.741 G＞A(E247K)、599delA、761delA、c.1148 C＞A(P383H)、c.1198 C＞T(R400C).2례환인행생동음식치료,3례여증가음식차수,료효현저,1례방기치료.결론 GLUT1-DS림상증상다양,이전(간)급다충발작성적림상증상위주요표현,기아여피로가유발림상증상적출현혹가중,차특점위본병중요적림상진단선색,이뇌척액당여혈당비치적강저시본병최위중요적림상진단의거.GLUT1-DS시가치성적신경계통질병,조진단、조치료가현저개선환인적예후.
Objective To analyze the clinical and SLC2A1 gene mutation characteristics of glucose transporter type 1 deficiency syndrome.Method The detailed clinical manifestations of six cases were recorded.The laboratory tests including EEG,MRI,blood chemistry,and lumbar puncture were performed.SLC2A1 gene mutations were analyzed by PCR,DNA sequencing and multiplex ligation-dependent probe amplification (MLPA).Result Patient 1,2 and 3 had classical clinical symptoms including infantile onset seizures,development delay.Patient 4,5 and 6 had non-classical clinical symptoms including paroxysmal behavior disturbance,weakness,ataxia,lethargy,especially after fasting or exercise,without severe seizures.The plasma glucose levels were normal.The CSF glucose levels decreased in all the six cases,ranged from 1.10 mmol/L to 2.45 mmol/L,the mean level was 1.68 mmol/L.The CSF glucose/plasma glucose ratios decreased,ranged from 0.16 to 0.51,the mean ratio was 0.34.Four patients had normal EEG.Two patients had focal and diffuse epileptiform discharge,and one of them also had paroxysmal occipital or generalized high-amplitude slow waves during awake and sleep time.MRI abnormalities were found in three patients,patient 1 with mild brain atrophy,patient 3 with bilateral ventricle plump,and patient 4 with high signals in T2 in the frontal and occipital white matter,interpreted as hypomyelination.SLC2A1 gene mutations were found in six cases.Patient 1 has large scale deletion in exon 2.In patient 2 to 6,the mutations were c.741 G＞A (E247K),599delA,761delA,c.1148 C ＞A (P383H),c.1198 C ＞T (R400C) respectively.Two patients were treated with ketogenic diet.The seizures disappeared and development became normal.Three patients responded to frequent meals with snacks.One patient refused any treatments,the symptoms continued to exist.Conclusion The clinical manifestations of glucose transporter type 1 deficiency syndrome are varied.The common symptoms included infantile onset seizures and various paroxysmal events.These neurologic symptoms generally fluctuated and were influenced by factors such as fasting or fatigue.This feature could be a very important clue for the diagnosis of GLUT1-DS.Lumbar puncture is recommended in patients with episodic CNS symptoms especially after fasting.GLUT1DS is a treatable neurometabolic disorder,early diagnosis and treatment may improve the prognosis of the patients.