Abstract

Spinocerebellar ataxia type 2 (SCA2) and amyotrophic lateral sclerosis (ALS) share a common molecular basis: both are associated with CAG-repeat expansion of ATXN2 and TDP-43-positive neuronal cytoplasmic inclusions. To date, the two disorders are viewed as clinically distinct with ALS resulting from 30-33 CAG-repeats and SCA2 from >34 CAG-repeats. We describe a 67-year old with a 32 CAG-repeat expansion of ATXN2 who presented with simultaneous symptoms of ALS and SCA2. Our case demonstrates that the clinical dichotomy between SCA2 and ATXN2-ALS is false. We suggest instead that CAG-repeat expansion length determines the timing of SCA2 clinical symptoms relative to onset of ALS; consistent with this age of onset of SCA2 but not ATXN2-ALS, is dependent upon expansion length. Review of the literature and our local cohort provides evidence for occurrence of ALS in late stage SCA2, which may be under-recognised by clinicians who think of the two diseases as distinct.

摘要

2型脊髓小脑共济失调（SCA2）和肌萎缩性侧索硬化症（ALS）具有共同的分子基础：两者均与ATXN2和TDP-43阳性神经元胞浆内含物的CAG重复扩增有关。迄今为止，这两种疾病被认为在临床上与30-33个CAG重复产生的ALS和> 34个CAG重复产生的SCA2在临床上不同。我们描述了一个67岁的ATXN2具有32个CAG重复扩增的人，该人同时出现ALS和SCA2症状。我们的案例表明，SCA2和ATXN2- ALS之间的临床二分法是错误的。相反，我们建议CAG重复扩展长度决定SCA2临床症状相对于ALS发作的时间。与此年龄的SCA2一致，但与ATXN2不一致-ALS，取决于扩展长度。对文献和我们当地队列的回顾提供了在SCA2晚期发生ALS的证据，认为这两种疾病截然不同的临床医生可能对此认识不足。