ATP1A3变异引起的急性神经炎症表现：三例不同表型患者的病例报告

文献信息

中文摘要

背景： ATP1A3变异可导致罕见的神经系统疾病，如儿童交替性偏瘫（AHC）、快速起病的肌张力障碍-帕金森综合征（RDP）以及小脑性共济失调-无反射-高弓足-视神经萎缩-感音神经性耳聋（CAPOS）。中间表型包括复发性脑病伴小脑性共济失调（RECA）和发热诱发的近端无力与脑病（FIPWE）。以急性脑病为临床表现并不常见。我们描述了三例携带ATP1A3变异的患者，他们以初始急性脑病就诊，这是一种不寻常的表现，旨在引起临床医生对这种较少为人知的临床表现的注意。
病例介绍： 在所有病例中，尽管MRI和脑脊液（CSF）检查正常，最初仍怀疑脑炎、吉兰-巴雷综合征或伴有共济失调的菱脑炎。最终，基因分析确定了ATP1A3变异，其中2例为Arg756变异。第一例是一名11岁女孩，表现为快速起病的四肢瘫痪、双侧面瘫、构音障碍、吞咽困难和肌张力障碍，最终诊断为RDP。第二例患者是一名21个月大的男孩，表现为急性小脑性共济失调、无力和无反射，在病毒感染后复发两次。最终诊断为RECA。第三例患者是一名3岁男孩，表现为急性四肢瘫痪、构音障碍、吞咽困难和癫痫发作。最终诊断为AHC。
结论： 当患者表现为自身免疫性脑炎或多神经根神经炎，但影像学和脑脊液分析正常，且对标准抗炎治疗无反应时，应考虑寻找ATP1A3基因突变。

英文摘要

BACKGROUND: ATP1A3 variants are responsible for rare neurological conditions such as Alternating Hemiplegia of Childhood (AHC), Rapid-onset Dystonia Parkinsonism (RDP), and Cerebellar Ataxia Areflexia Pes Cavus Optic Atrophy and Sensorineural Hearing Loss (CAPOS). Intermediate phenotypes include Relapsing Encephalopathy with Cerebellar Ataxia (RECA) and Fever-induced Proximal Weakness and Encephalopathy (FIPWE). Acute encephalopathy as a clinical presentation is unusual. We describe three patients with ATP1A3 variants who presented with initial acute encephalopathy, an unusual presentation, to draw clinicians' attention to this lesser-known clinical presentation.
CASE PRESENTATIONS: In all these cases, encephalitis, Guillain-Barré syndrome, or rhombencephalitis with ataxia were initially suspected, despite normal MRI and cerebrospinal fluid (CSF) findings. Ultimately, genetic analyses identified an ATP1A3 variant, including Arg756 variants in 2 cases. The first case is a 11-year-old girl with rapid-onset tetraparesis, facial diplegia, dysarthria, dysphagia, and dystonia, with a final diagnosis of RDP. The second patient is a 21-month-old boy who presented with acute cerebellar ataxia, weakness and areflexia, relapsing two times after viral infections. Final diagnosis was RECA. The third patient is a 3-year-old boy who presented with acute quadriplegia, dysarthria, dysphagia, and seizures. Final diagnosis was AHC.
CONCLUSION: When patients present with a picture of autoimmune encephalitis or polyradiculoneuritis with normal imaging and CSF analysis, and no response to standard anti-inflammatory treatment, a search for ATP1A3 gene mutations should be considered.