Autosomal recessive spastic ataxia of Charlevoix-Saguenay

A rare genetic disorder affecting the nervous system

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a rare genetic disorder characterized by a combination of spasticity, ataxia, and peripheral neuropathy. It was first described in the Charlevoix and Saguenay–Lac-Saint-Jean regions of Quebec, Canada.

Genetics

ARSACS is inherited in an autosomal recessive manner, meaning that an individual must inherit two copies of the mutated gene, one from each parent, to be affected by the disorder. The gene associated with ARSACS is the SACS gene, which encodes the protein sacsin. Mutations in this gene lead to the clinical manifestations of the disease.

Autosomal recessive inheritance pattern

Clinical Features

The clinical presentation of ARSACS typically begins in early childhood. The hallmark features include:

• Spasticity: Increased muscle tone and stiffness, particularly affecting the lower limbs, leading to difficulties with movement and coordination.
• Ataxia: A lack of voluntary coordination of muscle movements, resulting in gait abnormalities and balance issues.
• Peripheral neuropathy: Damage to the peripheral nerves, causing symptoms such as numbness, tingling, and muscle weakness.

Other symptoms may include dysarthria (difficulty speaking), nystagmus (involuntary eye movements), and retinal abnormalities.

Diagnosis

Diagnosis of ARSACS is based on clinical evaluation, family history, and genetic testing to identify mutations in the SACS gene. Magnetic resonance imaging (MRI) of the brain may show characteristic changes, such as atrophy of the cerebellum and brainstem.

Management

There is currently no cure for ARSACS, and treatment is primarily supportive. Management strategies may include:

• Physical therapy to improve mobility and reduce spasticity.
• Occupational therapy to assist with daily activities.
• Speech therapy for individuals with dysarthria.
• Orthopedic interventions, such as braces or surgery, to address musculoskeletal issues.

Prognosis

The progression of ARSACS is variable, but it generally leads to increasing disability over time. Life expectancy may be reduced, but many individuals live into adulthood.

Epidemiology

ARSACS is most prevalent in the Charlevoix and Saguenay–Lac-Saint-Jean regions of Quebec, where it is estimated to affect approximately 1 in 1,500 to 2,000 individuals. It is considered rare in other populations.

Related pages

• Ataxia
• Spasticity
• Peripheral neuropathy
• Genetic disorder