Comparison of the clinical and genetic features of amyotrophic lateral sclerosis across Cuban, Uruguayan and Irish clinic-based populations

Abstract

ObjectivesThis study compares the clinical characteristics of patients with amyotrophic lateral sclerosis (ALS) within three clinic-based populations from Cuba, Uruguay and Ireland and determines the impact of known ALS-associated genetic variants on phenotypic manifestations within the Cuban population.MethodsDemographic and clinical information was collected on 115 Cuban, 220 Uruguayan and 1038 Irish patients with ALS attending national specialist clinics through 1996–2017. All Cuban patients and 676 Irish patients underwent next-generation DNA sequencing and were screened for the pathogenic C9orf72 repeat expansion.ResultsThe mean age of onset was younger in the Cuban (53.0 years, 95% CI 50.4 to 55.6) and Uruguayan (58.2 years, 95% CI 56.5 to 60.0) populations compared with the Irish population (61.6 years, 95% CI 60.9 to 62.4). No differences in survival between populations were observed. 1.7 % (95% CI 0.6 to 4.1) of Cubans with ALS carried the C9orf72 repeat expansion compared with 9.9% (95% CI 7.8 to 12.0) of Irish patients with ALS (p=0.004). Other known variants identified in the Cuban population included ANG (one patient), CHCHD10 (one patient) and DCTN1 (three patients).Conclusions and relevanceThis study is the first to describe the clinical characteristics of ALS in Cuban and Uruguayan populations and report differences between the Cuban and Irish genetic signature in terms of known ALS-associated genetic variants. These novel clinical and genetic data add to our understanding of ALS across different and understudied populations.

Epidemiology of amyotrophic lateral sclerosis: an update of recent literature

“…Recent studies have shown that the mean or median age of ALS onset is between 51 and 66 years [1 ▪ ,3,4 ▪ ,5,6,7 ▪▪ ,18 ▪ ,19,20,23,26,28–31,32 ▪▪ ]. Patients in Europe have usually a later age at ALS onset compared with patients from China, Cuba, and Uruguay.…”

“…For example, Dorst et al [18 ▪ ] showed that Chinese ALS patients had a median age of ALS onset at 51 years, whereas the median age of ALS onset was around 10 years later among German ALS patients. Furthermore, the mean age at ALS onset was found to be 4–9 years smaller in Cuba and Uruguay compared with Ireland [26]. Population-based studies are more likely to include patients with the entire spectrum of disease characteristics, whereas clinic-based studies are more likely to include patients with specific characteristics (e.g., younger age at onset or slower disease progression) [33].…”

The Relationship between Selected Demographic Factors and Speech Organ Dysfunction in Sporadic ALS Patients

“…The men to women ratio in the study sample was 1.4, and the ratio described in the literature is 1-2 [19][20][21]. The mean age of ALS onset was 53.61 years (while the average is 51-66 years) [18,[21][22][23][24], and 68% of the patients had spinal disorders (literature average 58-82%) [25][26][27]. Such a distribution in a relatively large group of patients allows for drawing conclusions and transposing them to the general population of ALS patients.…”

The relationship between selected sociodemographic factors and speech organ dysfunction in sporadic ALS patients

“…The men to women ratio in the study sample was 1.4, and the ratio described in the literature is 1-2 [19][20][21]. The mean age of ALS onset was 53.61 years (while the average is 51-66 years) [18,[21][22][23][24], and 68% of the patients had spinal disorders (literature average 58-82%) [25][26][27]. Such a distribution in a relatively large group of patients allows drawing conclusions and transposing them to the general population of ALS patients.…”