Clinical characteristics in young-adult ALS – results from a Portuguese cohort study

Abstract

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.

Keywords:

• Amyotrophic lateral sclerosis
• young-adult ALS
• juvenile ALS
• genetic mutations
• prognosis
• survival

Declaration of interest

The authors reported no potential conflict of interest.

Additional information

Funding

This work was funded by Comprehensive evaluation of circulating MicroRNA as diagnostic and prognostic biomarkers in Amyotrophic Lateral Sclerosis [PTDC/MEC-NEU/31195/2017].