Autosomal recessive spastic ataxia of Charlevoix-Saguenay

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Autosomal recessive spastic ataxia of Charlevoix-Saguenay, more commonly known as ARSACS, is a condition affecting muscle movement. People with ARSACS typically have abnormal tensing of the muscles (spasticity), problems with balance and coordination (cerebellar ataxia), and reduced sensation and weakness in the arms and legs (peripheral neuropathy).

Additional muscle problems that can occur in ARSACS include muscle wasting (amyotrophy), involuntary eye movements (nystagmus), and difficulty swallowing (dysphagia) and speaking (dysarthria). Other features of ARSACS involve high-arched feet (pes cavus), a spine that curves to the side (scoliosis), yellow streaks of fatty tissue in the light-sensitive tissue at the back of the eye (hypermyelination of the retina), urinary tract problems, intellectual disability, hearing loss, and recurrent seizures (epilepsy).

An unsteady walking style (gait) is the first symptom of ARSACS. Walking problems usually begin between the ages of 12 months and 18 months, as toddlers are learning to walk. These movement problems worsen over time, with increased spasticity and ataxia of the arms and legs. In some cases spasticity goes away, but this apparent improvement is thought to be due to the wasting away (atrophy) of nerves in the arms and legs. Most affected individuals require wheelchair assistance by the time they are in their thirties or forties.

While this condition was named after the area in which it was first seen, the Charlevoix-Saguenay region of Quebec, Canada, ARSACS has been identified in individuals worldwide.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Mutations in the SACS gene cause ARSACS. The SACS gene provides instructions for producing a protein called sacsin. Sacsin is primarily found in cells in the brain, skin, and muscles used for movement (skeletal muscles), but the specific function of the protein is unknown. Research suggests that sacsin plays a role in organizing proteins into bundles called intermediate filaments. Intermediate filaments provide support and strength to cells. In nerve cells (neurons), specialized intermediate filaments called neurofilaments comprise the structural framework that establishes the size and shape of nerve cell extensions called axons, which are essential for transmission of nerve impulses to other neurons and to muscle cells.

Mutations in the SACS gene cause the production of an unstable sacsin protein that does not function normally. It is unclear how the abnormal sacsin protein affects the brain and skeletal muscles but it likely impairs normal organization of intermediate filaments in cells, particularly neurofilaments, and disrupts neuron function. This decreased neuronal signaling may result in the signs and symptoms of ARSACS.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

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.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

The incidence of ARSACS in the Charlevoix-Saguenay region is estimated to be 1 in 1,500 to 2,000 individuals. Outside of Quebec, the incidence of ARSACS is unknown. About 200 individuals with ARSACS have been described in the scientific literature.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Abnormal cerebellum morphology · Frequent (79-30%)

Any structural abnormality of the cerebellum.

Abnormal motor evoked potentials · Frequent (79-30%)

An anomaly identified by motor evoked potentials (MEPs). MEPs are measured following single-pulse or repetitive transcranial magnetic stimulation and can be used for the assessment of the excitability of the motor cortex and the integrity of conduction along the central and peripheral motor pathways.

Abnormal pyramidal sign · Frequent (79-30%)

Functional neurological abnormalities related to dysfunction of the pyramidal tract.

Abnormality of the cerebellar peduncle · Frequent (79-30%)

An anomaly of the cerebellar peduncles. The superior, middle, and inferior cerebellar peduncles emerge from the cerebellum. The superior cerebellar penduncles connect the cerebellum to the midbrain, the middle cerebellar peduncles connect the cerebellum to the pons, and the inferior cerebellar peduncle connects the medulla spinalis and medulla oblongata with the cerebellum.

Abnormality of the pons · Frequent (79-30%)

A structural abnormality of the pons.

Arachnoid cyst · Frequent (79-30%)

An extra-parenchymal and intra-arachnoidal collection of fluid with a composition similar to that of cerebrospinal fluid.

Ataxia · Frequent (79-30%)

Ataxia refers to impaired coordination of voluntary muscle movement. Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- or overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly).

Babinski sign · Frequent (79-30%)

Upturning of the big toe (and sometimes fanning of the other toes) in response to stimulation of the sole of the foot. If the Babinski sign is present it can indicate damage to the corticospinal tract.

Other findings in the same source

From: Orphanet

Additional reported features include Cerebellar atrophy (Frequent (79-30%)); Cerebellar vermis hypoplasia (Frequent (79-30%)); Demyelinating peripheral neuropathy (Frequent (79-30%)); Dysarthria (Frequent (79-30%)); Dysmetria (Frequent (79-30%)); Gait disturbance (Frequent (79-30%)); Gaze-evoked horizontal nystagmus (Frequent (79-30%)); Hypermyelinated retinal nerve fibers (Frequent (79-30%)); Hypoplasia of the corpus callosum (Frequent (79-30%)); Lower limb spasticity (Frequent (79-30%)). This is a selected summary, not a complete description of the condition.

Which doctor should you see?

The suggested department for discussing Autosomal recessive spastic ataxia of Charlevoix-Saguenay is Neurology, with a neurologist as the relevant type of clinician. General physician / Family Medicine; paediatrician for children. Referral depends on symptoms.

Additional services that may be relevant, depending on the findings, include: Clinical Genetics.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Which nervous-system findings help explain the symptoms?
• Would an assessment of walking, communication or daily function be helpful?
• Are rehabilitation or other specialist services relevant?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Autosomal recessive spastic ataxia of Charlevoix-Saguenay. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.