Clinical features and genetics of Amyotrophic Lateral Sclerosis
in Ecuador

Amyotrophic lateral sclerosis is a rare neurodegenerative disease that affects the motor neuron system. Motor neuron degeneration extends from the cortex to the anterior horns of the spinal cord. The disease is invariably fatal and the median survival time since diagnosis is around 15–20 months.

Recent original investigations and systematic reviews lead researchers to postulate the heterogeneity of ALS between geographic regions and populations. The difference in ALS occurrence and clinical characteristics could be related to differences in case ascertainment, health care system access, and variability of study design.
Nevertheless, these variations could be associated with the type and frequency of genetic mutations and the genetic ancestral origin of the populations.

The general aim of this project is to identify ALS phenotype and frequency of genetic mutations in relation to the ancestral origin in a predominant admixed population.

Patients with ALS will be identified in hospital centers from Quito, Guayaquil, and Cuenca (Ecuador) using a homogeneous methodology framework. Diagnosis will be based on the neurologist adjudication of Airlie House criteria: definite, probable, probable laboratory supported, or possible.

Demographic characteristics and clinical findings of ALS cases will be collected: age, sex, residency, family history of neurodegenerative disorders, date of first symptoms, type of onset, ALSFRS-R, Manual Muscular Testing, Airlie House criteria, symptoms, nutritional status, extrapyramidal signs, cognitive impairment assessed by the Edinburgh Cognitive and Behavioural ALS Screen (ECAS), other comorbidities.

Genotype testing of known ALS genes will be performed by next generation sequencing (C9orf72, SOD1, TARDBP, FUS). The molecular signature of ancestral origin will be assessed using genetic markers spread over the genome.

The project will provide reliable data on ALS phenotypes in a predominant admixed population and original data on the potential influence of genetic factors, especially the population’s ancestries, admixture, along with genetic mutations on ALS heterogeneity.

Multidisciplinary research based on multicenter international collaboration is essential to understand ALS.