Objective

Studies concerning young-adult amyotrophic lateral sclerosis (yALS) are uncommon, due to the rarity of this condition. We aimed to investigate this subject. Methods: A retrospective-prospective study was conducted in our ALS center, including 1278 ALS patients followed longitudinally. Patients were divided in two groups - yALS (onset ≤40 years) and adult-onset ALS (aALS, onset >40 years). We analyzed phenotype, survival and genetics. Results: Sixty-three out of 1278 (4.9%) patients were included in yALS group, while the majority were categorized as aALS (1215, 95.1%). Juvenile ALS (onset < 25 years) represented 14.3% (9 patients) of yALS. In yALS group mean onset age was 32.5 ± 6.6 years (14–40) and 68.3% were men. Spinal-onset was significantly more frequent in yALS (p < 0.001), while bulbar-onset was more common in aALS (p = 0.002). Diagnostic delay was longer in yALS group (p = 0.02). yALS patients survived longer than aALS (88.2 ± 81.9 versus 41.1 ± 34, p < 0.001), and functional decay was the only independent predictor found in the younger group (p = 0.007). No other significant differences were found, including familial history of ALS. Three yALS patients (4.8%) had C9orf72, SOD1 and FUS mutations identified by single-gene testing. A panel of 50 ALS-related genes investigated with next-generation sequencing in 9 yALS patients revealed no pathogenic mutation. Conclusions: yALS is a rare and specific ALS group. Disease progression is slower and survival longer in yALS, moreover and bulbar-onset phenotype is less common than in aALS. These observations are relevant to inform patients and for clinical trials design.

中文翻译：

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年轻成人 ALS 的临床特征 - 来自葡萄牙队列研究的结果。

客观的

由于这种情况很少见，有关年轻成人肌萎缩侧索硬化症 (yALS) 的研究并不常见。我们旨在调查这个主题。方法：在我们的 ALS 中心进行了一项回顾性-前瞻性研究，对 1278 名 ALS 患者进行了纵向跟踪。患者分为两组 - yALS（发病≤40 岁）和成人发病 ALS（aALS，发病 >40 岁）。我们分析了表型、存活率和遗传学。结果： 1278 名患者中有 63 名 (4.9%) 被纳入 yALS 组，而大多数被归类为 aALS (1215, 95.1%)。青少年 ALS（发病 < 25 岁）占 yALS 的 14.3%（9 名患者）。在 yALS 组中，平均发病年龄为 32.5 ± 6.6 岁（14-40 岁），68.3% 为男性。yALS 的脊椎发病率明显更高（p < 0.001)，而延髓起病在 aALS 中更常见 ( p  = 0.002)。yALS 组的诊断延迟更长（p  = 0.02）。yALS 患者的存活时间比 aALS 长（88.2 ± 81.9 对 41.1 ± 34，p  < 0.001），功能衰退是在年轻组中发现的唯一独立预测因子（p  = 0.007）。未发现其他显着差异，包括 ALS 家族史。三名 yALS 患者 (4.8%) 具有通过单基因检测鉴定的C9orf72、SOD1和FUS突变。在 9 名 yALS 患者中通过下一代测序研究了一组 50 个 ALS 相关基因，未发现致病突变。结论：yALS 是一种罕见且特殊的 ALS 组。yALS 的疾病进展较慢且生存期较长，而且延髓发病表型不如 aALS 常见。这些观察结果与告知患者和临床试验设计有关。