Background: A 38-year-old woman was diagnosed autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) with a novel pathogenic variant in the gene presented with gradually progressive spastic ataxia since the age of 2 years; then, she became wheelchair-bound at the age of 28 years.
Phenomenology: The patient presented a combination of cerebellar dysfunctions e.g., gaze-evoked nystagmus, scanning speech, finger dysmetria, and wide-based gait, lower limb spasticity, and typical funduscopic examination which was a hypermyelinated nerve fibers radiating from the optic disc.
Educational Value: At present, ARSACS is recognized as a rare, worldwide, inherited movement disorder in which we should to aware of a diagnosis of this disorder in the patient who is presented with gene negative early-onset spastic ataxia.
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| http://dx.doi.org/10.5334/tohm.68 | DOI Listing |
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Modeling sacsin depletion in Danio Rerio offers new insight on retinal defects in ARSACS.
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Department Neurobiology and Molecular Medicine, IRCCS Fondazione Stella Maris, 56128 Pisa, Italy. Electronic address:
Biallelic mutations in the SACS gene, encoding sacsin, cause early-onset autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS), a neurodegenerative disease also characterized by unique and poorly understood retinal abnormalities. While two murine models replicate the phenotypic and neuronal features observed in patients, no retinal phenotype has been described so far. In a zebrafish knock-out strain that faithfully mirrors the main aspects of ARSACS, we observed impaired visual function due to photoreceptor degeneration, likely caused by cell cycle defects in progenitor cells.
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Int J Mol Sci
December 2024
William Harvey Research Institute, Faculty of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK.
Mitochondrial dysfunction is implicated in the pathogenesis of the neurological condition autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS), yet precisely how the mitochondrial metabolism is affected is unknown. Thus, to better understand changes in the mitochondrial metabolism caused by loss of the sacsin protein (encoded by the SACS gene, which is mutated in ARSACS), we performed mass spectrometry-based tracer analysis, with both glucose- and glutamine-traced carbon. Comparing the metabolite profiles between wild-type and sacsin-knockout cell lines revealed increased reliance on aerobic glycolysis in sacsin-deficient cells, as evidenced by the increase in lactate and reduction of glucose.
View Article and Find Full Text PDFAutosomal-recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is an early-onset neurodegenerative disease caused by mutations in the SACS gene. The first two mutations were identified in French Canadian populations 20 years ago. The disease is now known as one of the most frequent recessive ataxias worldwide.
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Memory Clinic, Department of Neurology, Onze-Lieve-Vrouwziekenhuis, Aalst, Belgium.
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View Article and Find Full Text PDFLongitudinal Imaging Biomarkers Correlate with Progressive Motor Deficit in the Mouse Model of Charlevoix-Saguenay Ataxia.
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Division of Neuroscience, Mitochondrial Dysfunctions in Neurodegeneration, IRCCS Ospedale San Raffaele, Milan, Italy.
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