Objective: To describe the clinical presentation of 2 Mexican brothers diagnosed with autosomal recessive spastic ataxia of  Charlevoix-Saguenay (ARSACS) and compare their presentation with those reported in literature.

Background: Condition first described at 1978 in two areas at the east of Quebec, Canada: Charlevoix and Saguenay, by Dr. Bouchard et al. as an atypical form of Friedreich’s ataxia. ARSACS is an early onset neurodegenerative disorder, caused by a mutation in the SACS gene, located in 13q12, which codes for the Sacsin protein. The clinical presentation is characterized by cerebellar ataxia, spasticity, dysarthria, nystagmus, distal muscle weakness, alteration of conjugated eye movements, among others; as well as with an electromyographic pattern of denervation and decreased conduction velocity and imaging tests show atrophy of the cerebellum and spinal cord.

Method: From a series of 108 cases of recessive ataxias, 18 Friedreich ataxias, 38 mitochondrial cytopathies and some inborn errors of metabolism were diagnosed. In 40 cases with Friedreich-like syndrome, clinical exome sequencing was performed.

Results: Both siblings have a heredofamilial history of a father with cirrhosis and hepatocarcinoma, as well as a mother with leukemia at 36 years old. In both, molecular analyzes of the most frequent spinocerebellar ataxias were performed and the characteristic expansion of Friedreich’s Ataxia was ruled out, so they were considered as FRDA like until 2019. Subsequently the new generation sequencing (complete exome) revealed biallelic variations in SACS gene (variant 1 pathogenic, stop premature codon which generate the loss of 3301 amino acids at the C-terminal in the protein, highly deleterious mutation.Variant  2 probably pathogenic that generate a nucleotide change with substitution of tyrosine from aspartate).

Conclusion: Other cases of ARSACS associated with posterior fossa cysts have been described in a Brazilian family. Due to the differences reported in the literature and which was found in these cases, it is convenient to make a close phenotype-genotype correlation between the Franco-Canadian and Latino population to broaden the spectrum of alterations caused by ARSACS.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/autosomal-recessive-spastic-ataxia-of-charlevoix-saguenay-a-mexican-case-report/