Objective: Amyotrophic lateral sclerosis (ALS) is a rare worldwide heterogeneous neurodegenerative disease with sporadic and familial (FALS) forms. A rare autosomal dominant subtype of FALS was identified in a Brazilian family, classified as ALS type 8 (ALS8) linked to the VAPB gene. The aim of our study was to analyze a series of ALS8 patients from unrelated families in order to further characterize the disease. Methods: We reviewed only patients with probable or definite ALS according to the Awaji criteria being managed at a single center between 2004 and 2018 and with DNA samples available for genetic analysis. A retrospective analysis of clinical, laboratory, and electrophysiological features was performed, relevant data were recorded and DNA was analyzed to detect VAPB gene mutation. Results: Thirty-one ALS patients were eligible for genetic screening for ALS8 and the mutation was detected in five patients from unrelated families. The mean age of onset was 45 ± 5.3 years for the ALS8 group and 47.6 ± 13.1 years for the non-ALS8 group and the time between symptom onset and last follow-up was longer for ALS8 patients. Three patients in the ALS8 group had tremor (60%), four had pain in affected limb (80%) and all had cramps and abdominal protrusion. Conclusions: This study presents the largest series of ALS8 patients in southern Brazil. Our findings demonstrate several clinical features that may be characteristic of ALS8 and confirm that clinicians should suspect ALS8 when the clinical manifestations include cramps, abdominal protrusion, pain, and tremor.

目的：肌萎缩性侧索硬化症（ALS）是一种罕见的世界范围内的偶发性和家族性（FALS）形式的异质性神经退行性疾病。在巴西家庭中发现了罕见的FALS常染色体显性亚型，被分类为与VAPB基因相关的ALS 8型（ALS8）。我们的研究目的是分析来自无关家庭的一系列ALS8患者，以进一步表征该疾病。方法：我们仅根据2004年至2018年间由单一中心管理的Awaji标准，对患有ALS或明确ALS的患者进行了检查，并提供了可用于遗传分析的DNA样本。对临床，实验室和电生理特征进行了回顾性分析，记录了相关数据并分析了DNA以检测VAPB基因突变。结果：31例ALS患者符合进行ALS8基因筛查的资格，并且在5个无关家庭的患者中检测到该突变。ALS8组的平均发病年龄为45±5.3岁，非ALS8组的平均发病年龄为47.6±13.1岁，而ALS8患者的症状发作与最后随访之间的时间更长。ALS8组中有3例患有震颤（60％），四肢受累有疼痛（80％），均患有抽筋和腹部突出。结论：这项研究介绍了巴西南部最大的ALS8患者系列。我们的发现证明了ALS8可能具有的几种临床特征，并证实当临床表现包括抽筋，腹部突出，疼痛和震颤时，临床医生应怀疑ALS8。