Autosomal recessive spastic ataxia of Charlevoix–Saguenay: An overview

Assessment of Whole-Brain White Matter by DTI in Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay

“…2 In addition to developmental abnormalities in the TPF and their mechanical effects on the CST, axonal degeneration and, more extensively, demyelination in cerebral WM may explain a wide range of neurologic abnormalities other than spasticity and the progressive nature of the disease. Recently, Girard et al 30 showed localization of sacsin to mitochondria and a cascade of detrimental effects resulting in neuronal cell death by loss of sacsin function in knockout mice.…”

“…2 The responsible gene (SACS, MIM 604490) was located on chromosome 13q and encodes the sacsin protein, which is widely expressed throughout the brain with a predilection for pyramidal neurons, Purkinje cells, thalamic and pontine nuclei, and reticular formation. 3 Confusion with cerebral palsy and secondary spastic diplegia, and variations in the phenotype lead to underdiagnosis of ARSACS.…”

Hereditary ataxias: overview

“…Ataxia, dysarthria, spasticity, Review extensor plantar reflexes, distal muscle wasting, a distal sensorimotor neuropathy predominantly in the legs, and horizontal gaze nystagmus constitute the major neurologic signs, which are most often progressive. Yellow streaks of hypermyelinated fibers radiate from the edges of the optic fundi in the retina of Quebec-born individuals with autosomal recessive spastic ataxia of Charlevoix-Saguenay, 43 whereas the retinal changes are uncommon in French, Tunisian, and Turkish individuals with the condition. 44,45 Individuals with autosomal recessive spastic ataxia of Charlevoix-Saguenay become wheelchair bound at the average age of 41 years; cognitive skills are preserved long term, and individuals are able to accomplish activities of daily living late into adulthood.…”

Mitochondrial dynamics in neuronal injury, development and plasticity

“…Impaired mitochondrial fission has been observed in autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS), a neurodegenerative disease characterized by early-onset cerebellar ataxia and spasticity (Bouhlal et al, 2011). ARSACS results from loss-of-function mutations in the gene encoding sacsin, a huge protein thought to function as a Hsp70 co-chaperone (Parfitt et al, 2009).…”