常染色体隐性遗传性痉挛性共济失调一例并文献复习

Autosomal recessive spastic ataxia of Charlevoix Saguenay:a case report and literature review

目的探讨常染色体隐性遗传性痉挛性共济失调(autosomal recessive spastic ataxia of Charlevoix Saguenay,ARSACS)患者的临床、影像、病理及遗传学特点。方法选取2019年12月23日解放军总医院第六医学中心神经内科患者1例,回顾分析患者的临床、影像、腓肠神经活检病理及基因突变特点,并复习既往文献。结果本例患者男,21岁,2岁起病,首次发作表现为双下肢力弱及不耐受疲劳,11岁出现共济失调步态,17岁出现剪刀步态。主要临床表现为典型小脑共济失调、痉挛性截瘫和周围神经病“三联征”,头颅MRI示脑桥基底部和被盖部T2WI轴位横向条带状短T2信号,呈“4行2列”排列;脑桥小脑脚增粗,小脑上蚓部萎缩。神经电生理示运动神经潜伏期延长及波幅减低、传导速度减慢,感觉神经传导未检出确切波形。双侧胫骨前肌呈神经源性损害。腓肠神经活检病理示神经束内大、小有髓神经纤维密度中度减少,及散在分布的轴索变性及薄髓纤维。患者ARSACS基因存在p.D968Vfs*13和p.D1903Yfs*31的2处移码突变,分别来自患者父亲和母亲。既往文献未发现该突变报道,考虑为新发突变。结论ARSACS患者临床表现为典型“三联征”,头颅影像学表现为脑桥轴位T2WI呈“4行2列”排列的横向条带状短T2信号,腓肠神经活检呈慢性活动性轴索变性及髓鞘脱失,ARSACS基因新发突变。

Objective To explore the clinical,imaging,pathological and genetic features of autosomal recessive spastic ataxia of Charlevoix Saguenay(ARSACS).Methods A patient admitted to the Department of Neurology of the Sixth Medical Center of PLA General Hospital on December 23rd,2019 was selected.The clinical,imaging,sural nerve biopsy pathology and gene mutation characteristics of the patient were retrospectively analyzed,and the previous literature was reviewed.Results The patient was a 21-year-old male who got sick at the age of two,the first attack showed weakness of both lower limbs and fatigue intolerance,then ataxic gait at 11 years old,and scissors gait at 17 years old.The main clinical symptoms were typical triad of cerebellar ataxia,spastic paraplegia and peripheral neuropathy.Cranial MRI showed short T2 signals in transverse bands at the base of pons and tegmentum on T2WI axis,which were arranged in"four rows and two columns".The peduncle of cerebellar pontine increased and the vermis superior cerebellum atrophied.Neuroelectrophysiology results showed that the latency of motor nerve was prolonged,the amplitude was decreased,and the conduction speed was slowed down.No exact waveform was detected in sensory nerve conduction.Bilateral tibialis anterior results showed neurogenic damage.Pathology of sural nerve biopsy results showed that the density of large and small myelinated nerve fibers in the nerve bundle decreased moderately,and axonal degeneration and thin myelinated fibers were scattered.There were two frameshift mutations in ARSACS gene of the patient,namely p.D968Vfs*13 and p.D1903Yfs*31,which were found to be from the patients'father and mother respectively.This mutation was not reported in previous literatures and was considered to be a new mutation.Conclusions The clinical manifestations of the ARSACS patients are typical"triad".Cranial imaging shows transverse banded short T2 signals arranged in four rows and two columns on axial T2WI,biopsy of sural nerve shows chronic active axonal degeneration and myelin loss.New mutations are found in ARSACS gene.