Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a rare genetic disorder characterized by a specific type of spastic ataxia. It is an autosomal recessive condition, meaning an individual must inherit two copies of the defective gene (one from each parent) to manifest the disorder. It is named after the region in Quebec, Canada, where it was first identified.
Autosomal recessive spastic ataxia of Charlevoix-Saguenay genetic testing is included in Diagnostiki Athinon Monogenic Diseases Genetic Testing along with approximetaly 100 other inherited diseases, including cystic fibrosis (71 mutations) and hereditary breast cancer (genes BRCA1 415 mutations & BRCA2 419 mutations).
- Onset: Symptoms typically appear in early childhood or adolescence.
- Ataxia: Individuals with ARSACS experience ataxia, which is a lack of coordination and control of voluntary movements. This can affect various body parts, leading to problems with balance, walking, and hand-eye coordination.
- Spasticity: An increased muscle tone or spasticity results in stiffness and difficulty in moving specific muscles.
- Peripheral neuropathy: Some individuals with ARSACS may also develop peripheral neuropathy, which involves damage to the peripheral nerves and can lead to sensations of tingling or weakness in the limbs.
- Ophthalmological abnormalities: Abnormal eye movements and other eye-related issues may occur in individuals with ARSACS.
- Cerebellar atrophy: Neuroimaging studies often reveal atrophy (shrinkage) of the cerebellum, a brain region responsible for coordinating voluntary movements.
ARSACS is caused by mutations in the SACS gene located on chromosome 13. The SACS gene provides instructions for making a protein called sacsin, which plays a role in maintaining the health and function of nerve cells. Mutations in the SACS gene produce a defective sacsin protein, contributing to the symptoms associated with ARSACS. Sacsin is a co-chaperone that acts by regulating the activity of the chaperone Hsp70, which is essential for maintaining the correct folding of neuronal proteins. Chaperones, such as Hsp70, prevent the nervous system from accumulating misfolded proteins and neurodegeneration from occurring. It is suggested that sacsin protein may also be involved in microtubule organization, vesicle trafficking, and control of mitochondrial dynamics.
ARSACS is frequent in northeastern Quebec and is mainly caused by the c.8844del variant, detected in 96% of patients. More than 200 pathogenic mutations in the SACS gene are currently known to affect other countries such as Italy, Japan, Spain, and Turkey.
There is no cure for ARSACS, and treatment focuses on managing symptoms and providing supportive care. Genetic counseling is crucial for families with a history of ARSACS, as carriers of a single mutated gene may not exhibit symptoms but can pass the gene to their children.
This Genetic Test for Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay of Diagnostiki Athinon analyzes the five most frequent pathogenic mutations of the SACS gene.
With the technique used for genetic testing, only the gene's specific mutations, which are the most important and frequent in the literature, are analyzed. However, it should be noted that there are likely other gene or chromosomal mutations in the gene to be tested, which cannot be identified with this method. Different analysis techniques can be used for these cases, such as, e.g., next-generation sequencing (NGS).
