Spastic Ataxia, Charlevoix-Saguenay Type

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OMIM 57 270550 Disease Ontology 12 DOID:0050946 Orphanet 59 ORPHA98 UMLS via Orphanet 74 C1849140 ICD10 via Orphanet 34 G11.1 MESH via Orphanet 45 C536787

MedGen 42 C1849140 MeSH 44 D002524 KEGG 37 H01170 SNOMED-CT via HPO 69 258211005 75088002 165232002 563001 25786006 277843001 397803000 228156007 247578003 91138005 221360009 397790002 8011004 95646004 32566006 86854008 409712001 8074002 229844004 205091006 122481008 288939007 40739000 394679006 25136009 230233000 204043002 30721006 102935005 77420001 22631008 394616008 228158008 249942005 130980003 161898004 1912002 274818004 246586009 366575004 23414001 6077001 33595009 more UMLS 73 C1849140

NIH Rare Diseases : ⁵³ The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 98Disease definitionAutosomal 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.EpidemiologyIt 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.Clinical descriptionThe 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. 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.EtiologyARSACS is caused by autosomal recessive mutations in the SACS gene (13q11), which encodes a large protein of unknown function named sacsin.Diagnostic methodsClinical 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.Differential diagnosisDifferential diagnoses include other autosomal recessive ataxias, such as Friedreich ataxia and ataxia with vitamin E deficiency (AVED), and hereditary forms of spastic paraplegia (see these terms), in particular spastic paraplegia 20 (SPG20-Troyer syndrome).Antenatal diagnosisPrenatal diagnosis is possible when the disease-causing mutation has been identified and genetic counselling should be offered to affected families.Management and treatmentTreatment is symptomatic aiming towards controlling the spasticity and should include physiotherapy, pharmacotherapy and use of ankle-foot orthoses.PrognosisMost 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.Visit the Orphanet disease page for more resources.

MalaCards based summary : Spastic Ataxia, Charlevoix-Saguenay Type, also known as autosomal recessive spastic ataxia of charlevoix-saguenay, is related to spastic ataxia and spinocerebellar ataxia 31, and has symptoms including muscle spasticity, urgency of micturition and scanning speech. An important gene associated with Spastic Ataxia, Charlevoix-Saguenay Type is SACS (Sacsin Molecular Chaperone). Affiliated tissues include heart, eye and spinal cord, and related phenotypes are spasticity and dysarthria

OMIM : ⁵⁷ Autosomal recessive spastic ataxia of Charlevoix-Saguenay is a complex neurodegenerative disorder usually characterized by early childhood onset of cerebellar ataxia, pyramidal tract signs, and peripheral neuropathy. Most patients become wheelchair-bound; cognitive function is usually not affected. Some patients may have atypical features, such as later onset or initial presentation of peripheral neuropathy (summary by Baets et al., 2010). (270550)

UniProtKB/Swiss-Prot : ⁷⁵ Spastic ataxia Charlevoix-Saguenay type: A neurodegenerative disease characterized by early-onset cerebellar ataxia, spasticity, retinal hypermyelination, pyramidal signs, and both axonal and demyelinating neuropathy with loss of sensory nerve conduction and reduced motor conduction velocities. Other features include dysarthria, distal muscle wasting, nystagmus, defect in conjugate pursuit ocular movements, retinal striation (from prominent retinal nerves) obscuring the retinal blood vessels in places, and the frequent presence of mitral valve prolapse.

Genetics Home Reference : ²⁵ 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), difficulty coordinating movements (ataxia), muscle wasting (amyotrophy), involuntary eye movements (nystagmus), and speech difficulties (dysarthria). Other problems may include deformities of the fingers and feet, reduced sensation and weakness in the arms and legs (peripheral neuropathy), yellow streaks of fatty tissue in the light-sensitive tissue at the back of the eye (hypermyelination of the retina), and less commonly, leaks in one of the valves that control blood flow through the heart (mitral valve prolapse). An unsteady gait is the first symptom of ARSACS. It usually appears between the age of 12 months and 18 months, as toddlers are learning to walk. The signs and symptoms worsen over the years, with increased spasticity and ataxia of the arms and legs. In some cases spasticity disappears, but this apparent improvement is thought to be due to degeneration of nerves in the arms and legs. Most affected individuals require a wheelchair by the time they are in their thirties or forties.

Wikipedia : ⁷⁶ Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a very rare neurodegenerative... more...

GeneReviews: NBK1255

Clinical features from OMIM:

270550

#	Description	GenomeRNAi Source Accession	Score	Top Affiliating Genes
1	Increased shRNA abundance (Z-score > 2)	GR00366-A-103	9.47	SACS
2	Increased shRNA abundance (Z-score > 2)	GR00366-A-120	9.47	SACS
3	Increased shRNA abundance (Z-score > 2)	GR00366-A-126	9.47	SACS
4	Increased shRNA abundance (Z-score > 2)	GR00366-A-132	9.47	SACS
5	Increased shRNA abundance (Z-score > 2)	GR00366-A-195	9.47	SACS
6	Increased shRNA abundance (Z-score > 2)	GR00366-A-2	9.47	SACS
7	Increased shRNA abundance (Z-score > 2)	GR00366-A-36	9.47	SACS
8	Increased shRNA abundance (Z-score > 2)	GR00366-A-46	9.47	FXN SACS TTPA
9	Increased shRNA abundance (Z-score > 2)	GR00366-A-57	9.47	SACS
10	Increased shRNA abundance (Z-score > 2)	GR00366-A-76	9.47	TTPA
11	Increased shRNA abundance (Z-score > 2)	GR00366-A-85	9.47	FXN
12	Increased shRNA abundance (Z-score > 2)	GR00366-A-9	9.47	SACS

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