Abstract Details

Title Genetically Mediated ALS: Genotype-Phenotype Correlation and Disease Outcome in an Indian Cohort

Topic Neuromuscular and Clinical Neurophysiology (EMG)

Presentation(s) P11 - Poster Session 11 (8:00 AM-9:00 AM)

Poster/Presentation
Number 11-027

Objective

To describe genetic patterns, clinical phenotypes and disease outcome of Indian ALS patients.

Background Around 70% of familial and 10% of sporadic ALS forms are attributed to a known genetic cause. More than 40 genes are linked to ALS, highlighting heterogeneity in molecular basis of the disease. There are very few ALS genetics studies from India, the most populous and diverse country.

Design/Methods Retrospective analysis of genetically confirmed ALS cases evaluated between 2016 and 2023, who underwent Next Generation Sequencing (NGS). In 2024, patients were contacted telephonically to know disease outcome. The study was conducted at a tertiary care referral center for ALS.

Results We identified 47 individuals from 47 different families with genetically mediated ALS. 28 were sporadic and 19 were familial cases. 17 different genes were identified, among them SOD1 (11), C9orf72 (6), TARDBP (5), FUS (4), and OPTN (4) were common and other rare ones were SETX, CHCHD10, ERBB4, SPG11, CCNF, FIG4, MATR3, NEFH, NEK1, SIGMAR1, TUBA4A, VCP. Familial and sporadic cases had median age at onset of 43.0 and 49.5 years respectively, both groups had median duration of illness of 12 months. Overall, spinal onset of the disease was common (82.98%) than bulbar onset (17.02%). Mean survival time was greater in sporadic forms compared to familial ones (142.90 vs 77.30 months, CI 95%) however significance in difference of means couldn’t be proven due to less sample size. 4 patients had Juvenile forms of ALS with mutations in SOD1 (2/4, both homozygous), TARDBP (1/4), and FUS (1/4), with LMN predominant symptoms. 3 of them had rapid progression of illness with disease duration ranging from 8-15 months and died due to respiratory failure.

Conclusions

SOD1 mutations are the most common genetic cause of ALS. Familial forms had shorter survival. Larger studies are needed to know exact genetic spectrum of ALS in India.

Authors/Disclosures
Muddasu Suhasini Keerthipriya, MBBS PRESENTER	Dr. Keerthipriya has nothing to disclose.
Saraswati Nashi, MD (NIMHANS)	Dr. Nashi has nothing to disclose.
Priya Thomas, PhD	Dr. Thomas has nothing to disclose.
GAUTHAM ARUNACHAL, MD	Dr. ARUNACHAL has nothing to disclose.
Seena Vengalil, MD (Department of Neurology, NIMHANS)	Dr. Vengalil has nothing to disclose.
Nalini Atchayaram, MD, PhD	Prof. Atchayaram has nothing to disclose.

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