Salem Ikhlass Haj, Blais Mathieu, Zuluaga-Sánchez Valeria M, Rouleau Laurence, Becker Esther B E, Dupré Nicolas
Axe neurosciences du CHU de Québec - Université Laval, Quebec, QC, Canada.
Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom.
Cerebellum. 2025 Jan 3;24(1):24. doi: 10.1007/s12311-024-01777-9.
Autosomal-recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is an early-onset neurodegenerative disease caused by mutations in the SACS gene. The first two mutations were identified in French Canadian populations 20 years ago. The disease is now known as one of the most frequent recessive ataxias worldwide. Prominent features include cerebellar ataxia, pyramidal spasticity, and neuropathy. Neuropathological findings revealed cerebellar atrophy of the superior cerebellar vermis and the anterior vermis associated with Purkinje cell death, pyramidal degeneration, cortical atrophy, loss of motor neurons, and demyelinating neuropathy. No effective therapy is available for ARSACS patients but, in the last two decades, there have been significant advances in our understanding of the disease. New approaches in ARSACS, such as the reprogramming of induced pluripotent stem cells derived from patients, open exciting perspectives of discoveries. Several research questions are now emerging. Here, we review the clinical features of ARSACS as well as the cerebellar aspects of the disease, with an emphasis on recent fields of investigation.
夏尔勒沃-萨格奈常染色体隐性痉挛性共济失调（ARSACS）是一种由SACS基因突变引起的早发性神经退行性疾病。20年前在法裔加拿大人群中首次发现了前两个突变。该疾病现在被认为是全球最常见的隐性共济失调之一。突出特征包括小脑共济失调、锥体束痉挛和神经病变。神经病理学研究结果显示，小脑上蚓部和前蚓部萎缩，伴有浦肯野细胞死亡、锥体束变性、皮质萎缩、运动神经元丧失和脱髓鞘性神经病变。目前尚无针对ARSACS患者的有效治疗方法，但在过去二十年中，我们对该疾病的认识有了显著进展。ARSACS的新方法，如对患者来源的诱导多能干细胞进行重编程，开启了令人兴奋的发现前景。现在出现了几个研究问题。在此，我们回顾ARSACS的临床特征以及该疾病的小脑方面，重点关注最近的研究领域。
