General description

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a spinocerebellar degenerative disease associated with SACS gene abnormality characterized by prominent spasticity and hypermyelination of the retinal fibers.

The SACS gene is located on chromosome 13q12.12, which encodes the protein sacsin, a large modular protein essential for normal mitochondrial network organization. This protein demonstrates high expression levels in the central nervous system, particularly in motor neurons and cerebellar Purkinje cells, with additional presence in skin, skeletal muscles, and low levels in the pancreas.

On average, onset at around 5 years of age with gait difficulty and unsteadiness, progressive cerebellar ataxia, dysarthria, spastic paralysis, pathological reflexes, distal muscle atrophy and swan-neck-like hand deformities.

Originally reported as a disease of the Charlevoix-Saguenay region of Quebec, Canada, it was reported worldwide when the SACS gene was implicated. The clinical presentation of the disease became more diverse, with some cases not necessarily showing hypermyelination of the retinal fibers or spasticity.

References

1. Cocozza, Sirio, et al. "Conventional MRI findings in hereditary degenerative ataxias: a pictorial review." Neuroradiology 63.7 (2021): 983-999.
2. Prodi, E., et al. "Supratentorial and pontine MRI abnormalities characterize recessive spastic ataxia of C harlevoix‐S aguenay. A comprehensive study of an I talian series." European journal of neurology 20.1 (2013): 138-146.