ARSACS

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This entry is adapted from the peer-reviewed paper https://medlineplus.gov/genetics/condition/autosomal-recessive-spastic-ataxia-of-charlevoix-saguenay

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).

genetic conditions

1. Introduction

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.

2. Frequency

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.

3. Causes

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.

4. Inheritance

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.

5. Other Names for This Condition

ARSACS
Charlevoix-Saguenay spastic ataxia
spastic ataxia of Charlevoix-Saguenay
spastic ataxia, Charlevoix-Saguenay type

References

Engert JC, Bérubé P, Mercier J, Doré C, Lepage P, Ge B, Bouchard JP, MathieuJ, Melançon SB, Schalling M, Lander ES, Morgan K, Hudson TJ, Richter A. ARSACS, aspastic ataxia common in northeastern Québec, is caused by mutations in a newgene encoding an 11.5-kb ORF. Nat Genet. 2000 Feb;24(2):120-5.
Gagnon C, Desrosiers J, Mathieu J. Autosomal recessive spastic ataxia ofCharlevoix-Saguenay: upper extremity aptitudes, functional independence andsocial participation. Int J Rehabil Res. 2004 Sep;27(3):253-6.
Gagnon C, Lessard I, Lavoie C, Côté I, St-Gelais R, Mathieu J, Brais B. Anexploratory natural history of ataxia of Charlevoix-Saguenay: A 2-year follow-up.Neurology. 2018 Oct 2;91(14):e1307-e1311. doi: 10.1212/WNL.0000000000006290.
Grieco GS, Malandrini A, Comanducci G, Leuzzi V, Valoppi M, Tessa A, PalmeriS, Benedetti L, Pierallini A, Gambelli S, Federico A, Pierelli F, Bertini E,Casali C, Santorelli FM. Novel SACS mutations in autosomal recessive spasticataxia of Charlevoix-Saguenay type. Neurology. 2004 Jan 13;62(1):103-6.
Ouyang Y, Segers K, Bouquiaux O, Wang FC, Janin N, Andris C, Shimazaki H,Sakoe K, Nakano I, Takiyama Y. Novel SACS mutation in a Belgian family withsacsin-related ataxia. J Neurol Sci. 2008 Jan 15;264(1-2):73-6.
Richter AM, Ozgul RK, Poisson VC, Topaloglu H. Private SACS mutations inautosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) families from Turkey. Neurogenetics. 2004 Sep;5(3):165-70.
Takiyama Y. Autosomal recessive spastic ataxia of Charlevoix-Saguenay.Neuropathology. 2006 Aug;26(4):368-75.
Takiyama Y. Sacsinopathies: sacsin-related ataxia. Cerebellum.2007;6(4):353-9. doi: 10.1080/14734220701230466.
Vogel AP, Rommel N, Oettinger A, Stoll LH, Kraus EM, Gagnon C, Horger M, KrummP, Timmann D, Storey E, Schöls L, Synofzik M. Coordination and timing deficits inspeech and swallowing in autosomal recessive spastic ataxia ofCharlevoix-Saguenay (ARSACS). J Neurol. 2018 Sep;265(9):2060-2070. doi:10.1007/s00415-018-8950-4.

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Subjects: Genetics & Heredity

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Peter Tang

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Table of Contents

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1. Introduction

2. Frequency

3. Causes

4. Inheritance

5. Other Names for This Condition

References

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1. Introduction

2. Frequency

3. Causes

3.1. The gene associated with Autosomal recessive spastic ataxia of Charlevoix-Saguenay

4. Inheritance

5. Other Names for This Condition

References