亚历山大病Ⅱ型临床特点分析并文献复习  

Clinical analysis of type Ⅱ Alexander disease and literature review

作　　者：苗萌 张同霞[2] 李岩[3] 梁兵 赵玉英[2] 赵翠萍 焉传祝 Miao Meng;Zhang Tongxia;Li Yan;Liang Bing;Zhao Yuying;Zhao Cuiping;Yan Chuanzhu(Department of Neurology,Qilu Hospital of Shandong University(Qingdao),Qingdao 266035,China;Department of Neurology,Qilu Hospital of Shandong University,Jinan 250012,China;Department of Acupuncture-Moxibustion,Qilu Hospital of Shandong University,Jinan 250012,China)

机构地区：[1]山东大学齐鲁医院(青岛)神经内科,266035 [2]山东大学齐鲁医院神经内科,济南250012 [3]山东大学齐鲁医院针灸科,济南250012

出　　处：《中华神经科杂志》2021年第5期470-478,共9页Chinese Journal of Neurology

摘　　要：目的:分析亚历山大病Ⅱ型的临床特征、神经影像学表现及基因检测结果。方法:收集山东大学齐鲁医院(青岛)及山东大学齐鲁医院神经内科2018年8月至2020年6月收治的3例亚历山大病Ⅱ型患者的临床资料,对其临床及影像学资料进行回顾性分析。结果:3例患者均为中老年男性,隐匿起病,首发症状均为单下肢或双下肢无力,逐渐出现头晕、言语不清、吞咽困难、排尿困难、便秘、排汗异常及体位性低血压等症状,且症状呈进行性加重。3例患者在早期曾被误诊(分别被误诊为关节腔积液病、脑血管病、酒精中毒),颅脑磁共振成像(MRI)显示幕上白质病变轻,仅表现为侧脑室周围非特异性脑白质异常信号,延髓及上颈髓萎缩明显,呈“蝌蚪征”,有较高的提示价值。基因检测结果均为胶质纤维酸性蛋白基因单一杂合突变,且均为已报道的致病突变,分别为外显子6的c.1091C>T(p.A364V)杂合突变、外显子4的c.722C>T(p.R258C)杂合突变和外显子1的c.197G>A(p.R66Q)杂合突变。结论:亚历山大病Ⅱ型为常染色体显性遗传病,大部分为杂合点突变,少数为缺失突变。对于同时或逐渐出现头晕、球麻痹、自主神经功能障碍等脑干受累表现的患者,颅脑MRI显示幕上脑白质改变、延髓及上颈髓萎缩明显时,应考虑亚历山大病Ⅱ型可能。Objective To analyze the clinical features,imaging findings and gene test of patients with typeⅡAlexander disease.Methods All the clinical data of three cases with typeⅡAlexander disease from August 2018 to June 2020 in the Department of Neurology,Qilu Hospital of Shandong University(Qingdao)and Qilu Hospital of Shandong University were collected,and their clinical and imaging findings were analyzed retrospectively.Results All the three patients were middle aged and old men with a chronic progressive course,beginning with weakness of one or both lower limbs,followed by dizziness,dysarthria,dysphagia,sphincteral disturbances,constipation and orthostatic hypotension.Three patients all experienced misdiagnosis(hydrarthrosis,cerebral vascular disease,alcoholism,respectively)at early stage of the disease.Cranial magnetic resonance imaging(MRI)showed mild supratentorial periventricular leukodystrophy,which was not specific.Sagittal cranial MRI demonstrated medulla oblongata and upper cervical cord atrophy called“tadpole atrophy”,which had high suggestive value.The results of gene analysis showed heterozygous mutation of glial fibrillary acidic protein gene,which had been reported as pathogenic gene;c.1091C>T(p.A364V)in exon 6,c.722C>T(p.R258C)in exon 4 and c.197G>A(p.R66Q)in exon 1,respectively.Conclusions TypeⅡAlexander disease is an autosomal dominant disease,most with point mutations,rarely with deletion mutations.TypeⅡAlexander disease should be suspected when a patient had signs of lower brainstem involvement such as dizziness,ataxia,pyramidal sign,autonomic dysfunction,especially when cranial MRI showed mild supratentorial leukodystrophy,and medulla oblongata and upper cervical cord atrophy.

关 键 词：亚历山大病 胶质纤维酸性蛋白基因 延髓萎缩 脑白质病变 

分 类 号：R742[医药卫生—神经病学与精神病学]