ALG6基因变异致急性脑病1例报道及遗传学分析

A Case Report and Genetic Analysis of Acute Encephalopathy Caused by ALG6 Gene Variant

摘要: 目的：探讨1例以急性脑病起病的α-1,3-葡糖基转移酶(Alpha-1,3-glucosyltransferase, ALG6)基因变异患儿的临床特征和遗传学病因。方法：回顾分析一例ALG6基因变异患儿的临床资料，抽取患儿及其父母的外周血，采用二代测序方法进行家系全外显子、拷贝数变异、线粒体环基因检测，并采用Sanger测序验证。结果：患儿数次发生感染后急性脑病，表现为意识不清、胡言乱语、烦躁不安、不能进食、排尿困难、睡眠障碍，对症治疗数日后可恢复发病前水平，查体发现颈下黑棘皮，双侧乳头内陷，行为幼稚，韦氏智力测试IQ 33分，提示重度智力低下。辅助检查提示转氨酶升高、血清胆固醇及抗凝血酶Ⅲ降低；急性期脑脊液压力轻度升高，脑脊液常规、生化、病原学检查均正常；视频脑电：枕区背景活动稍慢；睡眠期小棘波发放；颅脑磁共振未见异常。医学全外显子检测显示患儿存在父源c.338G>A (p.Arg113His)和母源c.991del (p.Ser331Alafs*27)复合杂合变异。结论：反复发生感染后急性脑病表现，伴智力低下、感染期间血清转氨酶升高、乳头内陷，应考虑ALG6基因变异的可能，应尽早完善基因检查以明确诊断。

Abstract: Objective: To explore the clinical characteristics and genetic etiology of a child with acute encephalopathy as the initial presentation caused by Alpha-1,3-glucosyltransferase (ALG6) gene variation. Methods: The clinical data of a child with ALG6 gene variation were analyzed retrospectively. Peripheral blood samples were collected from the child and his/her parents. Next-generation sequencing (NGS) was used to detect family whole-exome sequencing (WES), copy number variation (CNV), and mitochondrial circular gene. Sanger sequencing was performed for verification. Results: The child experienced acute encephalopathy after infection on multiple occasions, presenting with disturbed consciousness, rambling speech, restlessness, inability to eat, dysuria, and sleep disorders. The child could recover to the pre-illness state after several days of symptomatic treatment. Physical examination revealed acanthosis nigricans below the neck, bilateral nipple retraction, and infantile behavior. The Wechsler Intelligence Scale test showed an IQ score of 33, indicating severe intellectual disability. Auxiliary examinations showed elevated transaminases, decreased serum cholesterol and antithrombin III. During the acute phase, the cerebrospinal fluid (CSF) pressure was significantly increased, while CSF routine, biochemical, and etiological examinations were all normal. Video electroencephalography (VEEG) showed slightly slow background activity in the occipital region and small spike waves during sleep. Cranial magnetic resonance imaging (MRI) showed no abnormalities. Medical whole-exome sequencing revealed that the child had compound heterozygous variations of paternal c.338G>A (p.Arg113His) and maternal c.991del (p.Ser331Alafs*27) in the ALG6 gene. Conclusion: For patients with recurrent acute encephalopathy after infection, accompanied by intellectual disability, elevated serum transaminases during infection, and nipple retraction, ALG6 gene variation should be considered, and genetic testing should be completed as early as possible to confirm the diagnosis.