Neurology Divison, Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas.
Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, Arkansas.
Pediatr Neurol. 2018 Oct;87:65-69. doi: 10.1016/j.pediatrneurol.2018.06.009. Epub 2018 Jul 4.
We describe a 13-year-old girl with a past medical history of epilepsy, intellectual impairment, dysphagia with gastric tube dependence, and autism spectrum disorder who presented with focal status epilepticus.
Video-electroencephalography revealed left occipital pseudoperiodic epileptiform discharges and frequent seizures originating from the left hemisphere. The seizure was refractory to antiepileptic medications and pharmacologic coma. Subsequently, left occipital lobectomy was done. Extensive evaluation including whole exome sequencing, histopathologic examination of brain and muscle samples, mitochondrial DNA content analysis of tissue sample was completed to detect the etiology.
Skeletal muscle mitochondrial DNA content (qPCR) analysis showed approximately 37% of the mean value of age and tissue matched control group consistent with a mitochondrial depletion syndrome. Microscopic examination of the brain showed cortical abnormalities that largely consisted of infarct-like pathology in a laminar manner, abnormalities of neuronal distribution, and white matter changes. Compound heterozygous mutations of the CARS2 gene were identified by whole exome sequencing; V52G variant [p.Val52Gly (GTG>GGG):c.155 T>G in exon 1] was inherited from the mother and T188M variant[p.Thr188Met (ACG>ATG): c.563 C>T in exon 5] was inherited from the father.
This is the first detailed clinicopathologic description of the Alpers-Huttenlocher syndrome phenotype from CARS mutations.
我们描述了一位 13 岁女孩，她既往有癫痫、智力障碍、吞咽困难伴胃管依赖和自闭症谱系障碍病史，表现为局灶性癫痫持续状态。
视频脑电图显示左侧枕叶假性周期性癫痫样放电和频繁的起源于左侧半球的癫痫发作。抗癫痫药物和药物诱导昏迷治疗无效。随后进行了左枕叶切除术。为了明确病因，进行了广泛的评估，包括全外显子组测序、脑和肌肉样本的组织病理学检查、组织样本中线粒体 DNA 含量分析。
骨骼肌线粒体 DNA 含量（qPCR）分析显示，大约有 37%的平均值低于年龄和组织匹配对照组，符合线粒体耗竭综合征。大脑的显微镜检查显示皮质异常，主要表现为层状梗死样病理学、神经元分布异常和白质改变。全外显子组测序发现 CARS2 基因的复合杂合突变；V52G 变异[p.Val52Gly (GTG>GGG): c.155 T>G 位于第 1 外显子]来自母亲，T188M 变异[p.Thr188Met (ACG>ATG): c.563 C>T 位于第 5 外显子]来自父亲。
这是首例由 CARS 突变引起的 Alpers-Huttenlocher 综合征表型的详细临床病理描述。
