Spastic ataxia Charlevoix-Saguenay type

Alternate names

SACS; Charlevoix-Saguenay spastic ataxia; Autosomal recessive spastic ataxia of Charlevoix-Saguenay; ARSACS; Spastic ataxia of Charlevoix-Saguenay

Definition

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a neurodegenerative disorder characterised by early-onset cerebellar ataxia with spasticity, a pyramidal syndrome and peripheral neuropathy.

Epidemiology

It was initially described in the Charlevoix-Saguenay region of Quebec where incidence of ARSACS at birth has been estimated at 1 in 1,932. The incidence and prevalence worldwide remain unknown but ARSACS is very rare in other countries with cases described from Turkey, Japan, The Netherlands, Italy, Belgium, France and Spain.

Cause

ARSACS is caused by autosomal recessive mutations in the SACS gene (13q11), which encodes a large protein of unknown function named sacsin.

Inheritance

Autosomal recessive inheritance, a 25% chance

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Onset

The age of onset in non-Quebec patients is variable (ranging from late infantile, juvenile to early-adult onset) but in individuals from Quebec, onset occurs between 12 and 18 months of age with gait disturbance and walking difficulties.

Signs and symptoms

• Other early signs of cerebellar ataxia include dysarthria and nystagmus.
• The spasticity is progressive and eventually dominates the clinical picture.
• The pyramidal syndrome is characterised by brisk patellar tendon reflexes and the Babinski sign.
• Onset of the peripheral neuropathy generally occurs later and leads to absence of the Achilles tendon reflex, distal amyotrophy and deep sensory disturbances (impaired vibration sense).
• Retinal hypermyelination (without vision loss) is a constant feature in ARSACS patients from Quebec but may be absent in patients from other countries.
• Lack of leg spasticity has been reported in some Japanese families and intellectual deficit may be a feature in some non-Quebec patients.
• Other manifestations may include mitral valve prolapse, pes cavus, and bladder dysfunction.

Diagnosis

• Clinical diagnosis relies on the results of neuroimaging studies (MRI and CT scans revealing atrophy of the upper cerebellar vermis and cervical spinal cord) and neurophysiological data (signs of both axonal and demyelinating neuropathy, with nerve conduction studies revealing loss of sensory nerve conduction and reduced motor conduction velocities).
• Retinal examination may also be useful for diagnosis.
• Diagnosis can be confirmed by detection of SACS mutations.

Antenatal diagnosis Prenatal diagnosis is possible when the disease-causing mutation has been identified and genetic counselling should be offered to affected families.

Treatment

Treatment is symptomatic aiming towards controlling the spasticity and should include physiotherapy, pharmacotherapy and use of ankle-foot orthoses.

Prognosis

Most patients become wheelchair-bound by the 5th decade of life. Death generally occurs during the sixth decade but survival into the seventies has been reported.

NIH genetic and rare disease info

• NIH info on Spastic ataxia Charlevoix-Saguenay type

Spastic ataxia Charlevoix-Saguenay type is a rare disease.

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