Oliveira Santos Miguel, Gromicho Marta, Pinto Susana, De Carvalho Mamede
Institute of Physiology, Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal.
Department of Neurosciences, and Mental Health, Hospital de Santa Maria, Centro Hospitalar Universitário de Lisboa Norte, Lisbon, Portugal.
Amyotroph Lateral Scler Frontotemporal Degener. 2020 Nov;21(7-8):620-623. doi: 10.1080/21678421.2020.1790611. Epub 2020 Jul 11.
Studies concerning young-adult amyotrophic lateral sclerosis (yALS) are uncommon, due to the rarity of this condition. We aimed to investigate this subject. 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. 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 ( < 0.001), while bulbar-onset was more common in aALS ( = 0.002). Diagnostic delay was longer in yALS group ( = 0.02). yALS patients survived longer than aALS (88.2 ± 81.9 versus 41.1 ± 34, < 0.001), and functional decay was the only independent predictor found in the younger group ( = 0.007). No other significant differences were found, including familial history of ALS. Three yALS patients (4.8%) had , and 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. 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.
由于青少年肌萎缩侧索硬化症（yALS）病例罕见，关于该病症的研究并不常见。我们旨在对这一课题展开调查。我们在肌萎缩侧索硬化症（ALS）中心开展了一项回顾性-前瞻性研究，纳入了1278例接受纵向随访的ALS患者。患者被分为两组——yALS（发病年龄≤40岁）和成人起病型ALS（aALS，发病年龄>40岁）。我们分析了其表型、生存率和遗传学特征。1278例患者中有63例（4.9%）被纳入yALS组，而大多数患者被归类为aALS（1215例，95.1%）。青少年型ALS（发病年龄<25岁）占yALS患者的14.3%（9例）。yALS组的平均发病年龄为32.5±6.6岁（14 - 40岁），男性占68.3%。yALS患者中脊髓起病型显著更为常见（<0.001），而延髓起病型在aALS中更为常见（=0.002）。yALS组的诊断延迟时间更长（=0.02）。yALS患者的生存期比aALS患者更长（88.2±81.9天对41.1±34天，<0.001），并且功能衰退是在较年轻组中发现的唯一独立预测因素（=0.007）。未发现其他显著差异，包括ALS家族史。通过单基因检测，3例yALS患者（4.8%）存在 、 和 突变。对9例yALS患者进行下一代测序，检测5族ALS相关基因，未发现致病突变。yALS是一个罕见且特殊的ALS组。yALS的疾病进展较慢，生存期更长，此外，延髓起病型表型比aALS少见。这些观察结果对于告知患者以及临床试验设计具有重要意义。
