Diagnostic challenges and clinico-genetic features in ARSACS: A case series.

Abstract

Background: Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a rare neurodegenerative disorder characterized by early-onset cerebellar ataxia, spasticity, and distal amyotrophy. This descriptive retrospective case series focuses on patients with ARSACS from the Indian subcontinent, with disease durations exceeding 10 years. Methods: This case series included patients with typical clinical features of ARSACS who were evaluated in a single neurology unit between 2016 and 2022. Data on age at onset, illness duration at the last follow-up, and clinical manifestations were recorded. Electrophysiology reports, neuroimaging findings, and genetic testing results were reviewed. Functional disability documented at the last available clinical evaluation was recorded. Results: The study comprised eight Indian patients with ARSACS [male/female (M:F) = 5:3] from unrelated families. The age at onset was between 2-5 years of age, with walking difficulties being the initial symptom in all cases. The correct diagnosis was established after the first decade of life, with a mean age at diagnosis of 23 years (range: 17-30 years) and a mean time to diagnosis of 20 years (range: 14-27 years). Electrophysiological studies showed demyelinating sensorimotor neuropathy. Imaging revealed characteristic linear T2-hypointensities in the pons and cerebellar atrophy. Genetic testing identified novel homozygous sacsin molecular chaperone (SACS) gene variants. Conclusion: This study provides valuable insights into the clinical and genetic features of ARSACS in the Indian subcontinent. The time taken to establish the diagnosis ranged from 14 to 27 years in this series. Recognizing characteristic clinical and imaging findings may facilitate earlier diagnosis. The identification of novel genetic variants further expands our understanding of ARSACS.