SPAX
MCID: SPS008
MIFTS: 41

Spastic Ataxia (SPAX)

Categories: Eye diseases, Genetic diseases, Metabolic diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Spastic Ataxia

MalaCards integrated aliases for Spastic Ataxia:

Name: Spastic Ataxia 12 58 36 29 54 6 15 71
Ataxia, Spastic 39
Spax 58

Classifications:

Orphanet: 58  
Rare neurological diseases


External Ids:

Disease Ontology 12 DOID:0050952
KEGG 36 H01351
ICD10 via Orphanet 33 G11.4
UMLS via Orphanet 72 C1849156
Orphanet 58 ORPHA316226
UMLS 71 C1849156

Summaries for Spastic Ataxia

KEGG : 36 Spastic ataxia (SPAX) is a heterogeneous group of progressive neurodegenerative disorders, characterized by lower-limb spasticity and generalized ataxia with dysarthria, impaired ocular movements, and gait disturbance. Mostly, mutations in the mitochondrial factors cause this disease.

MalaCards based summary : Spastic Ataxia, also known as ataxia, spastic, is related to spastic ataxia 1, autosomal dominant and spastic ataxia 2, autosomal recessive, and has symptoms including ataxia, dysdiadochokinesis and gait ataxia. An important gene associated with Spastic Ataxia is SPG7 (SPG7 Matrix AAA Peptidase Subunit, Paraplegin), and among its related pathways/superpathways is Aminoacyl-tRNA biosynthesis. Affiliated tissues include brain, spinal cord and eye, and related phenotypes are behavior/neurological and nervous system

Disease Ontology : 12 A hereditary ataxia that is characterized by early onset of cerebellar ataxia, pyramidal tract signs and peripheral neuropathy.

Related Diseases for Spastic Ataxia

Diseases in the Spastic Ataxia family:

Spastic Ataxia 1, Autosomal Dominant Spastic Ataxia 7, Autosomal Dominant
Spastic Ataxia 2, Autosomal Recessive Spastic Ataxia 3, Autosomal Recessive
Spastic Ataxia 4, Autosomal Recessive Spastic Ataxia 5, Autosomal Recessive
Spastic Ataxia 9, Autosomal Recessive Spastic Ataxia 1
Spastic Ataxia 2 Spastic Ataxia 3
Spastic Ataxia 4 Spastic Ataxia 5
Spastic Ataxia 7 Spastic Ataxia 8
Autosomal Dominant Spastic Ataxia Autosomal Recessive Spastic Ataxia

Diseases related to Spastic Ataxia via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 152)
# Related Disease Score Top Affiliating Genes
1 spastic ataxia 1, autosomal dominant 33.0 VAMP1 SAX1
2 spastic ataxia 2, autosomal recessive 32.8 KIF1C INCA1
3 spastic ataxia 3 32.8 MARS2 KIF1C
4 spastic ataxia 1 32.7 VAMP1 SAX1
5 spastic ataxia 8 32.6 POLR3A NKX6-2
6 spastic ataxia 4 32.6 SACS POLR3A MTPAP AFG3L2
7 spastic ataxia 2 32.6 MARS2 KIF1C KIF1A
8 spastic ataxia 5 32.6 SPG7 AFG3L2
9 autosomal recessive spastic ataxia 32.5 SGCG SACS KIF1C ANKFY1
10 ataxia, spastic, childhood-onset, autosomal recessive, with optic atrophy and mental retardation 31.9 SPG7 INCA1 HARS1
11 autosomal dominant cerebellar ataxia 31.8 SPG7 SACS CACNA1A AFG3L2
12 spasticity 31.2 SPG7 SACS KIF1A CAPN1 AFG3L2
13 paraplegia 30.9 SPG7 KIF1A GBA2 DDHD2 CAPN1
14 neuropathy 30.8 SPG7 SACS KIF1A HARS1 AFG3L2
15 spastic paraplegia 7, autosomal recessive 30.5 SPG7 AFG3L2
16 autosomal recessive cerebellar ataxia 30.5 SPG7 GBA2 CACNA1A
17 spastic paraplegia 54, autosomal recessive 30.5 SPG7 GBA2 DDHD2
18 hereditary ataxia 30.4 VAMP1 SPG7 SACS POLR3A CAPN1 CACNA1A
19 3-methylglutaconic aciduria, type iii 30.4 SPG7 SACS KIF1C AFG3L2
20 spastic paraplegia 76, autosomal recessive 30.3 KIF1C GBA2 CAPN1
21 spastic paraparesis 30.2 SPG7 MTPAP KIF1A GBA2 CHP1 CACNA1A
22 hereditary spastic paraplegia 30.2 SPG7 SACS KIF1C KIF1A INCA1 GBA2
23 spastic paraplegia 46, autosomal recessive 30.2 SPG7 KIF1C GBA2 DDHD2
24 early myoclonic encephalopathy 30.1 SPG7 CACNA1A AFG3L2
25 cerebellar disease 30.1 SPG7 SACS CACNA1A AFG3L2
26 spastic ataxia, charlevoix-saguenay type 11.9
27 spastic ataxia 4, autosomal recessive 11.7
28 spastic ataxia 5, autosomal recessive 11.6
29 spinocerebellar degeneration with macular corneal dystrophy, congenital cataracts, and myopia 11.6
30 spastic ataxia 8, autosomal recessive, with hypomyelinating leukodystrophy 11.6
31 spastic ataxia 3, autosomal recessive 11.5
32 spastic ataxia 9, autosomal recessive 11.5
33 spastic ataxia 7, autosomal dominant 11.4
34 spastic ataxia 7 11.3
35 cerebral amyloid angiopathy, itm2b-related, 1 11.2
36 oliver-mcfarlane syndrome 11.1
37 mitochondrial dna depletion syndrome 11.1
38 nkx6-2-related disorder 11.0
39 encephalopathy, progressive, with amyotrophy and optic atrophy 11.0
40 abri amyloidosis 11.0
41 autosomal dominant spastic ataxia 11.0
42 spastic ataxia-dysarthria due to glutaminase deficiency 11.0
43 ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia 10.9
44 cerebellar ataxia, early-onset, with retained tendon reflexes 10.9
45 ataxia and polyneuropathy, adult-onset 10.9
46 muscular dystrophy, limb-girdle, autosomal recessive 5 10.4 SGCG SACS
47 spastic paraplegia 27, autosomal recessive 10.4 MARS2 KIF1C
48 spinocerebellar ataxia, autosomal recessive 21 10.4 KIF1C GBA2
49 peripheral nervous system disease 10.4
50 hypomyelinating leukoencephalopathy 10.4 POLR3A KIF1C

Graphical network of the top 20 diseases related to Spastic Ataxia:



Diseases related to Spastic Ataxia

Symptoms & Phenotypes for Spastic Ataxia

UMLS symptoms related to Spastic Ataxia:


ataxia, dysdiadochokinesis, gait ataxia, muscle spasticity, cerebellar ataxia, ataxia, truncal

MGI Mouse Phenotypes related to Spastic Ataxia:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 9.73 AFG3L2 ANKFY1 CACNA1A CHP1 DDHD2 KIF1A
2 nervous system MP:0003631 9.36 AFG3L2 ANKFY1 CACNA1A CHP1 DDHD2 KIF1A

Drugs & Therapeutics for Spastic Ataxia

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Phenotypes, Biomarkers and Pathophysiology in Spastic Ataxias Not yet recruiting NCT04297891

Search NIH Clinical Center for Spastic Ataxia

Genetic Tests for Spastic Ataxia

Genetic tests related to Spastic Ataxia:

# Genetic test Affiliating Genes
1 Spastic Ataxia 29

Anatomical Context for Spastic Ataxia

MalaCards organs/tissues related to Spastic Ataxia:

40
Brain, Spinal Cord, Eye, Cerebellum

Publications for Spastic Ataxia

Articles related to Spastic Ataxia:

(show top 50) (show all 354)
# Title Authors PMID Year
1
A novel genomic disorder: a deletion of the SACS gene leading to spastic ataxia of Charlevoix-Saguenay. 61 54
18398442 2008
2
Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS): novel compound heterozygous mutations in the SACS gene. 61 54
18484239 2008
3
Neurophysiological study in a Spanish family with recessive spastic ataxia of Charlevoix-Saguenay. 54 61
17683082 2008
4
Sacsin-related ataxia (ARSACS): expanding the genotype upstream from the gigantic exon. 54 61
16606928 2006
5
A novel sacsin mutation in a Japanese woman showing clinical uniformity of autosomal recessive spastic ataxia of Charlevoix-Saguenay. 54 61
16421146 2006
6
Novel mutation of SACS gene in a Spanish family with autosomal recessive spastic ataxia. 54 61
16007637 2005
7
Structure of the XPC binding domain of hHR23A reveals hydrophobic patches for protein interaction. 54 61
15322280 2004
8
Phenotypic features and genetic findings in sacsin-related autosomal recessive ataxia in Tunisia. 54 61
12873855 2003
9
Rapid detection of the sacsin mutations causing autosomal recessive spastic ataxia of Charlevoix-Saguenay. 54 61
11788093 2001
10
Human genetics: lessons from Quebec populations. 54 61
11701644 2001
11
ARSACS, a spastic ataxia common in northeastern Québec, is caused by mutations in a new gene encoding an 11.5-kb ORF. 54 61
10655055 2000
12
Inherited Cerebellar Ataxias: 5-Year Experience of the Irish National Ataxia Clinic. 61
32816195 2021
13
Wiedemann-Rautenstrauch syndrome in an Indian patient with biallelic pathogenic variants in POLR3A. 61
33559318 2021
14
A novel SACS p.Pro4154GlnfsTer20 mutation in a family with autosomal recessive spastic ataxia of Charlevoix-Saguenay. 61
33559790 2021
15
Two cases of early-onset autosomal recessive spastic ataxia of Charlevoix-Saguenay diagnosed in adulthood. 61
33348119 2021
16
Two intronic cis-acting variants in both alleles of the POLR3A gene cause progressive spastic ataxia with hypodontia. 61
33491183 2021
17
Increasing involvement of CAPN1 variants in spastic ataxias and phenotype-genotype correlations. 61
33486633 2021
18
Wheelchair mobility, motor performance and participation of adult wheelchair users with ARSACS: a cross-sectional study. 61
33307884 2020
19
A novel PNPLA6 mutation in a Turkish family with intractable Holmes tremor and spastic ataxia. 61
33210227 2020
20
Documenting the psychometric properties of the scale for the assessment and rating of ataxia to advance trial readiness of Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay. 61
32736199 2020
21
Haemagglutinin displayed on the surface of Lactococcus lactis confers broad cross-clade protection against different H5N1 viruses in chickens. 61
33059676 2020
22
Analyzing Gene Expression Profiles from Ataxia and Spasticity Phenotypes to Reveal Spastic Ataxia Related Pathways. 61
32937819 2020
23
Measurement properties of wheelchair use assessment tools in adults with autosomal recessive spastic ataxia of Charlevoix-Saguenay. 61
32981404 2020
24
Absent Foveal Avascular Zone in Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay. 61
32991389 2020
25
Spinocerebellar ataxia type 48: last but not least. 61
32342324 2020
26
Interpretation challenges of novel dual-class missense and splice-impacting variant in POLR3A-related late-onset hereditary spastic ataxia. 61
32597037 2020
27
[Spastic ataxia of Charlevoix-Saguenay: Diagnosis made on fundus examination]. 61
32591161 2020
28
Recessive null-allele variants in MAG associated with spastic ataxia, nystagmus, neuropathy, and dystonia. 61
32629324 2020
29
A homozygous missense variant in the homeobox domain of the NKX6-2 results in progressive spastic ataxia type 8 associated with lower limb weakness and neurological manifestations. 61
32246862 2020
30
Pyrostigmine therapy in a patient with VAMP1-related congenital myasthenic syndrome. 61
32616363 2020
31
De novo mutations of TUBB2A cause infantile-onset epilepsy and developmental delay. 61
32203252 2020
32
Neurological Phenotypes Associated with AAAS-Related Disorders: Spastic Ataxia and Complex Spastic Paraplegia. 61
32146693 2020
33
Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay (ARSACS) in a Thai Patient: The Classic Clinical Manifestations, Funduscopic Feature, and Brain Imaging Findings with a Novel Mutation in the SACS Gene. 61
32775015 2020
34
De novo variants in CAMTA1 cause a syndrome variably associated with spasticity, ataxia, and intellectual disability. 61
32157189 2020
35
Development of Nanostructured Lipid Carriers for the Delivery of Idebenone in Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay. 61
32548430 2020
36
Biallelic Mutations in MTPAP Associated with a Lethal Encephalopathy. 61
31779033 2020
37
A novel AFG3L2 mutation close to AAA domain leads to aberrant OMA1 and OPA1 processing in a family with optic atrophy. 61
32600459 2020
38
Severe worsening of adult-onset Alexander disease after minor head trauma: Report of two patients and review of the literature. 61
32223977 2020
39
SACS Mutation-Positive Autosomal Recessive Spastic Ataxia of Charlevoix Saguenay (ARSACS) from Kerala. 61
32606540 2020
40
Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay (ARSACS): Case Report of a Novel Nonsense Mutation in the SACS Gene. 61
32606552 2020
41
CAPN1 and hereditary spastic paraplegia: a novel variant in an Iranian family and overview of the genotype-phenotype correlation. 61
32352326 2020
42
Expanding the clinical and neuroimaging features of NKX6-2-related hereditary spastic ataxia type 8. 61
32004679 2020
43
Autosomal recessive spastic ataxia of charlevoix-saguenay: Findings from MRI in two adult Italian siblings. 61
32140197 2020
44
Docosahexaenoic acid in ARSACS: observations in two patients. 61
32466761 2020
45
Expanding the clinical and genetic heterogeneity of SPAX5. 61
32237276 2020
46
Novel frameshift mutation in the SACS gene causing spastic ataxia of charlevoix-saguenay in a consanguineous family from the Arabian Peninsula: A case report and review of literature. 61
32368540 2020
47
Spastic ataxia with eye-of-the-tiger-like sign in 4 siblings due to novel compound heterozygous AFG3L2 mutation. 61
32248051 2020
48
Clinical Features and Molecular Genetics of Autosomal Recessive Ataxia in the Turkish Population. 61
33042236 2020
49
A VPS13D spastic ataxia mutation disrupts the conserved adaptor-binding site in yeast Vps13. 61
31943017 2020
50
VPS13D-related disorders presenting as a pure and complicated form of hereditary spastic paraplegia. 61
31876103 2020

Variations for Spastic Ataxia

ClinVar genetic disease variations for Spastic Ataxia:

6
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 SPG7 NM_003119.4(SPG7):c.1990_1992del (p.Gln664del) Deletion Pathogenic 625204 rs1597665063 16:89620253-89620255 16:89553845-89553847
2 HARS1 NM_002109.6(HARS1):c.616G>T (p.Asp206Tyr) SNV Pathogenic 804285 rs1131040 5:140057507-140057507 5:140677922-140677922
3 HARS1 NM_002109.6(HARS1):c.730delG Deletion Pathogenic 804286 rs1581505917 5:140057005-140057005 5:140677420-140677420
4 SPG7 NM_003119.4(SPG7):c.1529C>T (p.Ala510Val) SNV Pathogenic 42016 rs61755320 16:89613145-89613145 16:89546737-89546737
5 INCA1 NM_006612.6(KIF1C):c.864+1G>A SNV Likely pathogenic 560374 rs1567721108 17:4907212-4907212 17:5003917-5003917
6 CACNA1A NM_001127222.2(CACNA1A):c.4997G>A (p.Arg1666Gln) SNV Uncertain significance 585575 rs1568447650 19:13346498-13346498 19:13235684-13235684
7 KCNMA1 NM_001161352.2(KCNMA1):c.1361C>A (p.Ala454Asp) SNV Uncertain significance 373984 rs1057518815 10:78846325-78846325 10:77086567-77086567

Expression for Spastic Ataxia

Search GEO for disease gene expression data for Spastic Ataxia.

Pathways for Spastic Ataxia

Pathways related to Spastic Ataxia according to KEGG:

36
# Name Kegg Source Accession
1 Aminoacyl-tRNA biosynthesis hsa00970

GO Terms for Spastic Ataxia

Cellular components related to Spastic Ataxia according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrion GO:0005739 9.56 VAMP1 SPG7 SACS MTPAP MARS2 HARS1
2 axon cytoplasm GO:1904115 9.33 SPG7 KIF1C KIF1A
3 m-AAA complex GO:0005745 8.62 SPG7 AFG3L2

Biological processes related to Spastic Ataxia according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrial calcium ion transmembrane transport GO:0006851 9.37 SPG7 AFG3L2
2 cytoskeleton-dependent intracellular transport GO:0030705 9.32 KIF1C KIF1A
3 mitochondrial fusion GO:0008053 9.26 SPG7 AFG3L2
4 mitochondrial protein processing GO:0034982 9.16 SPG7 AFG3L2
5 retrograde neuronal dense core vesicle transport GO:1990049 8.96 KIF1C KIF1A
6 anterograde neuronal dense core vesicle transport GO:1990048 8.62 KIF1C KIF1A

Molecular functions related to Spastic Ataxia according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 ATP binding GO:0005524 9.8 SPG7 MTPAP MARS2 KIF1C KIF1A HARS1
2 ATPase activity GO:0016887 9.26 SPG7 KIF1C KIF1A AFG3L2
3 ATP-dependent microtubule motor activity, plus-end-directed GO:0008574 9.16 KIF1C KIF1A
4 ATP-dependent peptidase activity GO:0004176 8.62 SPG7 AFG3L2

Sources for Spastic Ataxia

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Mar-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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