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HEREDITARY MONOGENIC DISEASES

           

Autosomal recessive spastic ataxia of Charlevoix-Saguenay

Neuromuscular Autosomal Recessive Spastic Ataxia Charlevoix-Saguenay (ARSACS) is a neurodegenerative disorder characterized by early cerebellar ataxia with neuromuscular disorders, pyramidal syndrome and peripheral neuropathy.

It was initially described in the Charlevoix-Saguenay of Quebec, where the incidence of ARSACS at birth was estimated at 1 / 1,932 but the carrier frequency is 1/22 in the Charlevoix-Saguenay-Lac-Saint-Jean (CSLSJ) region of Quebec. There are cases described from Turkey, Japan, The Netherlands, Italy, Belgium, France and Spain.

The incidence and global prevalence remain unknown. In patients who are not from Quebec, the age when ARSACS manifests varies between late childhood to youth, until early adulthood, however, individuals of Quebec begins between 12 and 18 months of age with disorders and difficulties in gait.

Other early symptoms of cerebellar ataxia include dysarthria and nystagmus.

Neuromuscular disorders progress until they dominate the clinical picture. The pyramidal syndrome is characterized by rapid tendon reflexes of knee bone and Babinski signs.

The onset of peripheral neuropathy generally occurs later, leading to the absence of reflexes in the Achilles tendon, distal muscular dystrophy and severe sensory disturbances (impaired vibration sense).

A constant feature in patients ARSACS of Quebec is the hypermielinization of the retina (without loss of vision), but absent in patients from other countries.

In some affected Japanese families it has detected the absence of neuromuscular disorders in the legs, and for some of the patients from outside of Quebec, intellectual deficit may be a feature. Other manifestations of this disease may include mitral valve prolapse, pes cavus, and bladder dysfunction.

ARSACS is caused by an autosomal recessive mutation in the SACS gene (13q11) encoding a long chain protein of unknown function and which bears sacsina name.

The clinical diagnosis depends on both the results of neuroimaging studies and the neurophysiological data. Among the first, magnetic resonance imaging and computed tomography show atrophy in the top of the cerebellar vermis and cervical spinal cord end, while neurophysiological studies reveal signs of neuropathy of axons and demyelination. There are other studies indicating a loss of sensory nerve-conduction as well as a reduction in the driving speed signal of the motor nerves. It may also be useful to include an examination of the retina recognition in diagnosis. This can be confirmed by the detection of SACS mutations.

The differential diagnosis include other types of autosomal recessive ataxias such as Friedreich’s ataxia, ataxia of vitamin E deficiency (AVED), hereditary forms of paraplegia by neuromuscular disorders, especially paraplegia 20 (SPG20 or Troyer syndrome).

Genetic counseling is needed to affected families that have been able to identify the causative mutation of this disease.

Symptomatic treatment is aimed at relieving neuromuscular disorders and should include physiotherapy, pharmacotherapy and use of orthopaedic systems for the foot and ankles. Most patients remain in wheelchair into the fifth decade of life. Death usually happens during the sixth decade, although there are cases of survival in the seventh.

Neuromuscular disorders progress until they dominate the clinical picture. The pyramidal syndrome is characterized by rapid tendon reflexes of knee bone and Babinski signs.

The onset of peripheral neuropathy generally occurs later, leading to the absence of reflexes in the Achilles tendon, distal muscular dystrophy and severe sensory disturbances (impaired vibration sense).

A constant feature in patients ARSACS of Quebec is the hypermielinization of the retina (without loss of vision), but absent in patients from other countries.

In some affected Japanese families it has detected the absence of neuromuscular disorders in the legs, and for some of the patients from outside of Quebec, intellectual deficit may be a feature. Other manifestations of this disease may include mitral valve prolapse, pes cavus, and bladder dysfunction.

ARSACS is caused by an autosomal recessive mutation in the SACS gene (13q11) encoding a long chain protein of unknown function and which bears sacsina name.

The clinical diagnosis depends on both the results of neuroimaging studies and the neurophysiological data. Among the first, magnetic resonance imaging and computed tomography show atrophy in the top of the cerebellar vermis and cervical spinal cord end, while neurophysiological studies reveal signs of neuropathy of axons and demyelination. There are other studies indicating a loss of sensory nerve-conduction as well as a reduction in the driving speed signal of the motor nerves. It may also be useful to include an examination of the retina recognition in diagnosis. This can be confirmed by the detection of SACS mutations.

The differential diagnosis include other types of autosomal recessive ataxias such as Friedreich’s ataxia, ataxia of vitamin E deficiency (AVED), hereditary forms of paraplegia by neuromuscular disorders, especially paraplegia 20 (SPG20 or Troyer syndrome).

Genetic counseling is needed to affected families that have been able to identify the causative mutation of this disease.

Symptomatic treatment is aimed at relieving neuromuscular disorders and should include physiotherapy, pharmacotherapy and use of orthopaedic systems for the foot and ankles. Most patients remain in wheelchair into the fifth decade of life. Death usually happens during the sixth decade, although there are cases of survival in the seventh.

GENE OR REGION STUDIED


  • SACS