MCID: SPS150
MIFTS: 37

Spastic Ataxia, Charlevoix-Saguenay Type

Categories: Genetic diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Spastic Ataxia, Charlevoix-Saguenay Type

MalaCards integrated aliases for Spastic Ataxia, Charlevoix-Saguenay Type:

Name: Spastic Ataxia, Charlevoix-Saguenay Type 54 13 69
Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay 56 71
Spastic Ataxia Charlevoix-Saguenay Type 71 29
Charlevoix-Saguenay Spastic Ataxia 12 14
Arsacs 56 71
Spax6 56 71
Autosomal Recessive Spastic Ataxia Type 6 56
Spastic Ataxia 6, Autosomal Recessive 71
Sacs 71

Characteristics:

Orphanet epidemiological data:

56
autosomal recessive spastic ataxia of charlevoix-saguenay
Inheritance: Autosomal recessive; Age of onset: Childhood;

OMIM:

54
Inheritance:
autosomal recessive

Miscellaneous:
later onset has been reported
most patients become wheelchair-bound
onset usually in infancy or early childhood
high prevalence in charlevoix-saguenay region of northeastern quebec
estimated carrier frequency in charlevoix-saguenay region is 1/22


HPO:

32
spastic ataxia, charlevoix-saguenay type:
Onset and clinical course infantile onset
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 56  
Rare neurological diseases


Summaries for Spastic Ataxia, Charlevoix-Saguenay Type

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.

MalaCards based summary : Spastic Ataxia, Charlevoix-Saguenay Type, also known as autosomal recessive spastic ataxia of charlevoix-saguenay, is related to endolymphatic sac tumor and arsacs, and has symptoms including nystagmus, dysarthria and distal sensory impairment. An important gene associated with Spastic Ataxia, Charlevoix-Saguenay Type is SACS (Sacsin Molecular Chaperone). Affiliated tissues include heart, eye and retina, and related phenotype is Increased shRNA abundance (Z-score > 2).

OMIM : 54
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 : 71 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.

Related Diseases for Spastic Ataxia, Charlevoix-Saguenay Type

Graphical network of the top 20 diseases related to Spastic Ataxia, Charlevoix-Saguenay Type:



Diseases related to Spastic Ataxia, Charlevoix-Saguenay Type

Symptoms & Phenotypes for Spastic Ataxia, Charlevoix-Saguenay Type

Symptoms via clinical synopsis from OMIM:

54

Head And Neck- Eyes:
nystagmus
impaired smooth pursuit
retinal striation
hypermyelinated retinal fibers

Genitourinary- Bladder:
urinary urgency

Muscle Soft Tissue:
distal muscle weakness due to peripheral neuropathy

Skeletal- Hands:
swan neck-like deformities of the fingers

Neurologic- Central Nervous System:
dysarthria
hyperreflexia
spasticity
extensor plantar responses
distal muscle weakness
more
Skeletal- Feet:
pes cavus
hammertoes

Neurologic- Peripheral Nervous System:
loss of large myelinated fibers
decreased sensory nerve conduction velocities (ncv)
distal sensory loss, especially vibratory sense
decreased motor ncv


Clinical features from OMIM:

270550

Human phenotypes related to Spastic Ataxia, Charlevoix-Saguenay Type:

32 (show all 28)
id Description HPO Frequency HPO Source Accession
1 nystagmus 32 HP:0000639
2 dysarthria 32 HP:0001260
3 distal sensory impairment 32 HP:0002936
4 hyperreflexia 32 HP:0001347
5 spasticity 32 HP:0001257
6 intellectual disability 32 HP:0001249
7 urinary urgency 32 HP:0000012
8 pes cavus 32 HP:0001761
9 falls 32 HP:0002527
10 distal muscle weakness 32 HP:0002460
11 impaired smooth pursuit 32 HP:0007772
12 dysmetria 32 HP:0001310
13 decreased nerve conduction velocity 32 HP:0000762
14 spastic ataxia 32 HP:0002497
15 scanning speech 32 HP:0002168
16 distal amyotrophy 32 HP:0003693
17 babinski sign 32 HP:0003487
18 progressive gait ataxia 32 HP:0007240
19 cerebellar vermis atrophy 32 HP:0006855
20 swan neck-like deformities of the fingers 32 HP:0006150
21 loss of purkinje cells in the cerebellar vermis 32 HP:0007001
22 hammertoe 32 HP:0001765
23 impaired vibration sensation in the lower limbs 32 HP:0002166
24 absent achilles reflex 32 HP:0003438
25 decreased number of large peripheral myelinated nerve fibers 32 HP:0003387
26 decreased sensory nerve conduction velocity 32 HP:0003448
27 progressive truncal ataxia 32 HP:0007221
28 hypermyelinated retinal nerve fibers 32 HP:0007922

UMLS symptoms related to Spastic Ataxia, Charlevoix-Saguenay Type:


muscle spasticity, scanning speech

GenomeRNAi Phenotypes related to Spastic Ataxia, Charlevoix-Saguenay Type according to GeneCards Suite gene sharing:

26
id Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Increased shRNA abundance (Z-score > 2) GR00366-A-103 9.44 SACS
2 Increased shRNA abundance (Z-score > 2) GR00366-A-120 9.44 SACS
3 Increased shRNA abundance (Z-score > 2) GR00366-A-126 9.44 SACS
4 Increased shRNA abundance (Z-score > 2) GR00366-A-132 9.44 SACS
5 Increased shRNA abundance (Z-score > 2) GR00366-A-2 9.44 SACS
6 Increased shRNA abundance (Z-score > 2) GR00366-A-36 9.44 SACS
7 Increased shRNA abundance (Z-score > 2) GR00366-A-46 9.44 FXN SACS TTPA
8 Increased shRNA abundance (Z-score > 2) GR00366-A-57 9.44 SACS
9 Increased shRNA abundance (Z-score > 2) GR00366-A-76 9.44 TTPA
10 Increased shRNA abundance (Z-score > 2) GR00366-A-85 9.44 FXN
11 Increased shRNA abundance (Z-score > 2) GR00366-A-9 9.44 SACS

Drugs & Therapeutics for Spastic Ataxia, Charlevoix-Saguenay Type

Interventional clinical trials:


id Name Status NCT ID Phase Drugs
1 Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford Recruiting NCT01793168

Search NIH Clinical Center for Spastic Ataxia, Charlevoix-Saguenay Type

Genetic Tests for Spastic Ataxia, Charlevoix-Saguenay Type

Genetic tests related to Spastic Ataxia, Charlevoix-Saguenay Type:

id Genetic test Affiliating Genes
1 Spastic Ataxia Charlevoix-Saguenay Type 29

Anatomical Context for Spastic Ataxia, Charlevoix-Saguenay Type

MalaCards organs/tissues related to Spastic Ataxia, Charlevoix-Saguenay Type:

39
Heart, Eye, Retina

Publications for Spastic Ataxia, Charlevoix-Saguenay Type

Variations for Spastic Ataxia, Charlevoix-Saguenay Type

UniProtKB/Swiss-Prot genetic disease variations for Spastic Ataxia, Charlevoix-Saguenay Type:

71 (show all 24)
id Symbol AA change Variation ID SNP ID
1 SACS p.Asp168Tyr VAR_064801
2 SACS p.Thr201Lys VAR_064802
3 SACS p.Leu308Phe VAR_064803
4 SACS p.Leu556Pro VAR_064804
5 SACS p.Leu802Pro VAR_064805
6 SACS p.Cys991Arg VAR_064806
7 SACS p.Phe1054Ser VAR_064807 rs137853019
8 SACS p.Met1311Lys VAR_064808
9 SACS p.Arg1575Pro VAR_064809
10 SACS p.His1587Arg VAR_064810
11 SACS p.Trp1946Arg VAR_064811 rs137853017
12 SACS p.Arg2703Cys VAR_064813 rs780332615
13 SACS p.Pro2798Gln VAR_064814 rs140551762
14 SACS p.Trp3248Arg VAR_064816 rs137853018
15 SACS p.Leu3481Pro VAR_064817
16 SACS p.Arg3636Gln VAR_064818 rs281865119
17 SACS p.Leu3645Pro VAR_064819
18 SACS p.Pro3652Thr VAR_064820 rs201505036
19 SACS p.Phe3653Ser VAR_064821
20 SACS p.Ala4074Pro VAR_064822 rs137853016
21 SACS p.Arg4331Gln VAR_064823 rs773009784
22 SACS p.Glu4343Lys VAR_064824 rs749383532
23 SACS p.Lys4508Thr VAR_064825
24 SACS p.Asn4549Asp VAR_064826

ClinVar genetic disease variations for Spastic Ataxia, Charlevoix-Saguenay Type:

6 (show top 50) (show all 105)
id Gene Variation Type Significance SNP ID Assembly Location
1 SACS NM_014363.5(SACS): c.8844delT (p.Ile2949Phefs) deletion Pathogenic rs281865117 GRCh37 Chromosome 13, 23909171: 23909171
2 SACS NM_014363.5(SACS): c.7504C> T (p.Arg2502Ter) single nucleotide variant Pathogenic rs281865118 GRCh37 Chromosome 13, 23910511: 23910511
3 SACS NM_014363.5(SACS): c.12220G> C (p.Ala4074Pro) single nucleotide variant Pathogenic rs137853016 GRCh37 Chromosome 13, 23905795: 23905795
4 SACS SACS, 1-BP DEL, 1411T deletion Pathogenic
5 SACS SACS, 1-BP INS, 1155A insertion Pathogenic
6 SACS NM_014363.5(SACS): c.5836T> C (p.Trp1946Arg) single nucleotide variant Pathogenic rs137853017 GRCh37 Chromosome 13, 23912179: 23912179
7 SACS NM_014363.5(SACS): c.4033dupC (p.Gln1345Profs) duplication Pathogenic rs606231163 GRCh38 Chromosome 13, 23339843: 23339843
8 SACS NM_014363.5(SACS): c.9742T> C (p.Trp3248Arg) single nucleotide variant Pathogenic rs137853018 GRCh37 Chromosome 13, 23908273: 23908273
9 SACS NM_014363.5(SACS): c.3161T> C (p.Phe1054Ser) single nucleotide variant Pathogenic rs137853019 GRCh37 Chromosome 13, 23914854: 23914854
10 SACS SACS, 10-BP DEL, NT32627 deletion Pathogenic
11 SACS SACS, 1-BP DEL, 31760T deletion Pathogenic
12 SACS NM_014363.5(SACS): c.10907G> A (p.Arg3636Gln) single nucleotide variant Pathogenic rs281865119 GRCh37 Chromosome 13, 23907108: 23907108
13 SACS NM_014363.5(SACS): c.12160C> T (p.Gln4054Ter) single nucleotide variant Pathogenic/Likely pathogenic rs281865120 GRCh37 Chromosome 13, 23905855: 23905855
14 SACS NM_014363.5(SACS): c.3589T> C (p.Ser1197Pro) single nucleotide variant Likely pathogenic rs727503785 GRCh37 Chromosome 13, 23914426: 23914426
15 SACS NM_014363.5(SACS): c.12973C> T (p.Arg4325Ter) single nucleotide variant Likely pathogenic rs762947018 GRCh38 Chromosome 13, 23330903: 23330903
16 SACS NM_014363.5(SACS): c.12851_12854delAGAG (p.Glu4284Alafs) deletion Likely pathogenic rs786204628 GRCh37 Chromosome 13, 23905161: 23905164
17 SACS NM_014363.5(SACS): c.12232C> T (p.Arg4078Ter) single nucleotide variant Likely pathogenic rs141315518 GRCh37 Chromosome 13, 23905783: 23905783
18 SACS NM_014363.5(SACS): c.10466_10467delCT (p.Ser3489Leufs) deletion Likely pathogenic rs786204416 GRCh37 Chromosome 13, 23907548: 23907549
19 SACS NM_014363.5(SACS): c.7276C> T (p.Arg2426Ter) single nucleotide variant Likely pathogenic rs786204750 GRCh37 Chromosome 13, 23910739: 23910739
20 SACS NM_014363.5(SACS): c.3328dupA (p.Ile1110Asnfs) duplication Likely pathogenic rs773840580 GRCh37 Chromosome 13, 23914687: 23914687
21 SACS NM_014363.5(SACS): c.2439_2440delAT (p.Val815Glyfs) deletion Likely pathogenic rs775059063 GRCh37 Chromosome 13, 23915575: 23915576
22 SACS NM_014363.5(SACS): c.13527dupA (p.Glu4510Argfs) duplication Pathogenic rs797045936 GRCh37 Chromosome 13, 23904488: 23904488
23 SACS NM_014363.5(SACS): c.10906C> T (p.Arg3636Ter) single nucleotide variant Pathogenic/Likely pathogenic rs780247476 GRCh37 Chromosome 13, 23907109: 23907109
24 SACS NM_014363.5(SACS): c.1919_1920delAC (p.His640Profs) deletion Pathogenic rs797045937 GRCh38 Chromosome 13, 23354692: 23354693
25 SACS NM_014363.5(SACS): c.8848_8849dupCA (p.Val2951Metfs) duplication Likely pathogenic rs797044608 GRCh37 Chromosome 13, 23909166: 23909167
26 SACS NM_014363.5(SACS): c.8542_8543delTT (p.Phe2848Profs) deletion Pathogenic rs876657721 GRCh37 Chromosome 13, 23909472: 23909473
27 SACS NM_014363.5(SACS): c.7641dupA (p.Glu2548Argfs) duplication Pathogenic rs876657720 GRCh37 Chromosome 13, 23910374: 23910374
28 SACS NM_014363.5(SACS): c.9508C> T (p.Arg3170Ter) single nucleotide variant Pathogenic/Likely pathogenic rs202199411 GRCh37 Chromosome 13, 23908507: 23908507
29 SACS NM_014363.5(SACS): c.12028C> T (p.Gln4010Ter) single nucleotide variant Pathogenic rs148297332 GRCh37 Chromosome 13, 23905987: 23905987
30 SACS NM_014363.5(SACS): c.13283dupA (p.Tyr4428Terfs) duplication Likely pathogenic rs1057517123 GRCh37 Chromosome 13, 23904732: 23904732
31 SACS NM_014363.5(SACS): c.13132C> T (p.Arg4378Ter) single nucleotide variant Likely pathogenic rs747868017 GRCh37 Chromosome 13, 23904883: 23904883
32 SACS NM_014363.5(SACS): c.12923_12927delAAGAA (p.Lys4308Serfs) deletion Likely pathogenic rs1057517294 GRCh37 Chromosome 13, 23905088: 23905092
33 SACS NM_014363.5(SACS): c.12540delA (p.Glu4180Aspfs) deletion Likely pathogenic rs1057516347 GRCh38 Chromosome 13, 23331336: 23331336
34 SACS NM_014363.5(SACS): c.11731delA (p.Ser3911Alafs) deletion Likely pathogenic rs1057517232 GRCh38 Chromosome 13, 23332145: 23332145
35 SACS NM_014363.5(SACS): c.11374C> T (p.Arg3792Ter) single nucleotide variant Likely pathogenic rs565203731 GRCh37 Chromosome 13, 23906641: 23906641
36 SACS NM_014363.5(SACS): c.11247_11250delCAAT (p.Asn3750Thrfs) deletion Likely pathogenic rs753205260 GRCh37 Chromosome 13, 23906765: 23906768
37 SACS NM_014363.5(SACS): c.11185C> T (p.Gln3729Ter) single nucleotide variant Likely pathogenic rs1057516398 GRCh38 Chromosome 13, 23332691: 23332691
38 SACS NM_014363.5(SACS): c.11081dupG (p.Cys3694Trpfs) duplication Likely pathogenic rs1057516856 GRCh37 Chromosome 13, 23906934: 23906934
39 SACS NM_014363.5(SACS): c.11042dupA (p.Phe3682Valfs) duplication Likely pathogenic rs756597098 GRCh37 Chromosome 13, 23906973: 23906973
40 SACS NM_014363.5(SACS): c.10864C> T (p.Gln3622Ter) single nucleotide variant Likely pathogenic rs1057516578 GRCh37 Chromosome 13, 23907151: 23907151
41 SACS NM_014363.5(SACS): c.10854delA (p.Glu3619Lysfs) deletion Likely pathogenic rs1057516773 GRCh37 Chromosome 13, 23907161: 23907161
42 SACS NM_014363.5(SACS): c.10804C> T (p.Gln3602Ter) single nucleotide variant Likely pathogenic rs1057517002 GRCh37 Chromosome 13, 23907211: 23907211
43 SACS NM_014363.5(SACS): c.10686_10689delCTTT (p.Phe3562Leufs) deletion Likely pathogenic rs779338945 GRCh37 Chromosome 13, 23907326: 23907329
44 SACS NM_014363.5(SACS): c.10497C> A (p.Tyr3499Ter) single nucleotide variant Likely pathogenic rs755186798 GRCh37 Chromosome 13, 23907518: 23907518
45 SACS NM_014363.5(SACS): c.10136T> G (p.Leu3379Ter) single nucleotide variant Likely pathogenic rs1057517250 GRCh38 Chromosome 13, 23333740: 23333740
46 SACS NM_014363.5(SACS): c.10090delG (p.Ala3364Leufs) deletion Likely pathogenic rs1057517383 GRCh37 Chromosome 13, 23907925: 23907925
47 SACS NM_014363.5(SACS): c.9818_9831delATACTCTAAAAGAC (p.Asp3273Valfs) deletion Likely pathogenic rs1057516464 GRCh37 Chromosome 13, 23908184: 23908197
48 SACS NM_014363.5(SACS): c.9390_9391delTA (p.His3130Glnfs) deletion Likely pathogenic rs1057517349 GRCh38 Chromosome 13, 23334485: 23334486
49 SACS NM_014363.5(SACS): c.9377dupT (p.Leu3128Thrfs) duplication Likely pathogenic rs1057516875 GRCh38 Chromosome 13, 23334499: 23334499
50 SACS NM_014363.5(SACS): c.9088_9089dupTT (p.Leu3030Phefs) duplication Likely pathogenic rs1057517060 GRCh37 Chromosome 13, 23908926: 23908927

Expression for Spastic Ataxia, Charlevoix-Saguenay Type

Search GEO for disease gene expression data for Spastic Ataxia, Charlevoix-Saguenay Type.

Pathways for Spastic Ataxia, Charlevoix-Saguenay Type

GO Terms for Spastic Ataxia, Charlevoix-Saguenay Type

Biological processes related to Spastic Ataxia, Charlevoix-Saguenay Type according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 cellular response to hydrogen peroxide GO:0070301 8.62 FXN SETX

Sources for Spastic Ataxia, Charlevoix-Saguenay Type

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