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 3, and has symptoms including ataxia, dysdiadochokinesis and gait ataxia. An important gene associated with Spastic Ataxia is HARS1 (Histidyl-TRNA Synthetase 1), and among its related pathways/superpathways is Aminoacyl-tRNA biosynthesis. Affiliated tissues include brain, spinal cord and testes, and related phenotype is behavior/neurological.

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 181)
# Related Disease Score Top Affiliating Genes
1 spastic ataxia 1, autosomal dominant 34.7 VAMP1 SAX1
2 spastic ataxia 3 34.4 MARS2 KIF1C
3 spastic ataxia 1 34.3 VAMP1 SAX1
4 autosomal recessive spastic ataxia 34.2 SGCG SACS KIF1C
5 spastic ataxia 5 34.2 SPG7 AFG3L2
6 spastic ataxia 4 34.2 POLR3A MTPAP AFG3L2
7 spastic ataxia 2 34.1 MARS2 KIF1C KIF1A
8 spastic ataxia 8 33.8 POLR3A NKX6-2 GJC2
9 autosomal dominant cerebellar ataxia 32.4 SPG7 SACS CACNA1A AFG3L2
10 leukodystrophy, hypomyelinating, 7, with or without oligodontia and/or hypogonadotropic hypogonadism 32.3 POLR3A GJC2
11 spasticity 31.0 SPG7 SACS KIF1A CAPN1
12 spastic paraplegia 7, autosomal recessive 30.7 SPG7 SACS AFG3L2
13 peripheral nervous system disease 30.7 SACS KIF1A HARS1 CACNA1A
14 hypomyelinating leukodystrophy 30.4 POLR3A NKX6-2 GJC2
15 spastic paraplegia 54, autosomal recessive 30.3 SPG7 GBA2 DDHD2
16 autosomal recessive cerebellar ataxia 30.3 SPG7 SACS GBA2 CACNA1A
17 cerebellar disease 30.3 SACS CACNA1A AFG3L2
18 spinocerebellar ataxia 28 30.2 SPG7 AFG3L2
19 spastic paraplegia 76, autosomal recessive 30.1 KIF1C GBA2 CAPN1
20 spastic paraparesis 30.1 SPG7 MTPAP KIF1A CHP1 CACNA1A
21 alacrima, achalasia, and mental retardation syndrome 30.1 KIF1C HARS1 GJC2 CACNA1A
22 hereditary ataxia 30.0 VAMP1 SPG7 SACS POLR3A CAPN1 CACNA1A
23 spastic paraplegia 46, autosomal recessive 29.9 SPG7 KIF1C GBA2 DDHD2
24 paraplegia 29.9 SPG7 KIF1A GJC2 GBA2 DDHD2 CAPN1
25 hereditary spastic paraplegia 29.1 SPG7 SACS KIF1C KIF1A GJC2 GBA2
26 spastic ataxia, charlevoix-saguenay type 12.9
27 spastic ataxia 4, autosomal recessive 12.7
28 spastic ataxia 5, autosomal recessive 12.7
29 spastic ataxia 8, autosomal recessive, with hypomyelinating leukodystrophy 12.6
30 spastic ataxia 3, autosomal recessive 12.6
31 spastic ataxia 2, autosomal recessive 12.6
32 spastic ataxia 9, autosomal recessive 12.5
33 spastic ataxia 7, autosomal dominant 12.4
34 spastic ataxia 7 12.4
35 spinocerebellar degeneration with macular corneal dystrophy, congenital cataracts, and myopia 12.3
36 autosomal dominant spastic ataxia 12.2
37 spastic ataxia-dysarthria due to glutaminase deficiency 12.2
38 behr syndrome 11.9
39 nkx6-2-related disorder 11.5
40 cerebral amyloid angiopathy, itm2b-related, 1 11.5
41 multiple sclerosis 11.4
42 ataxia, spastic, childhood-onset, autosomal recessive, with optic atrophy and mental retardation 11.4
43 pelizaeus-merzbacher-like disease 11.4
44 leukoencephalopathy with vanishing white matter 11.3
45 megalencephalic leukoencephalopathy with subcortical cysts 1 11.3
46 leukoencephalopathy, progressive, with ovarian failure 11.3
47 oliver-mcfarlane syndrome 11.2
48 leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation 11.2
49 cerebroretinal microangiopathy with calcifications and cysts 1 11.2
50 cerebroretinal microangiopathy with calcifications and cysts 2 11.2

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:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 9.44 AFG3L2 CACNA1A CHP1 DDHD2 GJC2 KIF1A

Drugs & Therapeutics for Spastic Ataxia

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Cross-sectional Descriptive Study to Quantify to What Extent Activity Capacity, Performance and Body Composition Predict Day to Day Life Participation in Ambulatory Children With CP. Completed NCT01217242
2 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, Testes, Eye, Cerebellum, T Cells

Publications for Spastic Ataxia

Articles related to Spastic Ataxia:

(show top 50) (show all 331)
# Title Authors PMID Year
1
A novel genomic disorder: a deletion of the SACS gene leading to spastic ataxia of Charlevoix-Saguenay. 54 61
18398442 2008
2
Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS): novel compound heterozygous mutations in the SACS gene. 54 61
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. 61 54
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. 61 54
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
De novo mutations of TUBB2A cause infantile-onset epilepsy and developmental delay. 61
32203252 2020
13
Biallelic Mutations in MTPAP Associated with a Lethal Encephalopathy. 61
31779033 2020
14
Neurological Phenotypes Associated with AAAS-Related Disorders: Spastic Ataxia and Complex Spastic Paraplegia. 61
32146693 2020
15
De novo variants in CAMTA1 cause a syndrome variably associated with spasticity, ataxia, and intellectual disability. 61
32157189 2020
16
Development of Nanostructured Lipid Carriers for the Delivery of Idebenone in Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay. 61
32548430 2020
17
Expanding the clinical and neuroimaging features of NKX6-2-related hereditary spastic ataxia type 8. 61
32004679 2020
18
Autosomal recessive spastic ataxia of charlevoix-saguenay: Findings from MRI in two adult Italian siblings. 61
32140197 2020
19
Severe worsening of adult-onset Alexander disease after minor head trauma: Report of two patients and review of the literature. 61
32223977 2020
20
Docosahexaenoic acid in ARSACS: observations in two patients. 61
32466761 2020
21
CAPN1 and hereditary spastic paraplegia: a novel variant in an Iranian family and overview of the genotype-phenotype correlation. 61
32352326 2020
22
Spinocerebellar ataxia type 48: last but not least. 61
32342324 2020
23
Spastic ataxia with eye-of-the-tiger-like sign in 4 siblings due to novel compound heterozygous AFG3L2 mutation. 61
32248051 2020
24
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
25
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
26
Expanding the clinical and genetic heterogeneity of SPAX5. 61
32237276 2020
27
A VPS13D spastic ataxia mutation disrupts the conserved adaptor-binding site in yeast Vps13. 61
31943017 2020
28
VPS13D-related disorders presenting as a pure and complicated form of hereditary spastic paraplegia. 61
31876103 2020
29
History of Multiple Sclerosis in Iran. 61
32126791 2020
30
Ophthalmological changes in hereditary spastic paraplegia and other genetic diseases with spastic paraplegia. 61
31865189 2020
31
POLR3A-related spastic ataxia: new mutations and a look into the phenotype. 61
31637490 2020
32
Genetic and phenotypic characterization of NKX6-2-related spastic ataxia and hypomyelination. 61
31509304 2020
33
[Spastic ataxia of Charlevoix-Saguenay: the first Russian case report and literature review]. 61
32307416 2020
34
Spastic ataxia associated with colour vision deficiency due to DDHD2 mutations. 61
31532039 2020
35
Childhood-onset autosomal recessive ataxias: a cross-sectional study from Turkey. 61
31741144 2020
36
Complicated paroxysmal kinesigenic dyskinesia associated with SACS mutations. 61
32055599 2020
37
Cerebello-Cortical Alterations Linked to Cognitive and Social Problems in Patients With Spastic Paraplegia Type 7: A Preliminary Study. 61
32161564 2020
38
CAPN1 mutations: Expanding the CAPN1-related phenotype: From hereditary spastic paraparesis to spastic ataxia. 61
30572172 2019
39
Defining the clinical-genetic and neuroradiological features in SPG54: description of eight additional cases and nine novel DDHD2 variants. 61
31302745 2019
40
Short Review: Investigating ARSACS: models for understanding cerebellar degeneration. 61
30636067 2019
41
Development and validation of a disease severity index for ataxia of Charlevoix-Saguenay. 61
31534027 2019
42
The "broken wishbone" splenial sign: A diagnostic hallmark for SPG54 spastic ataxia. 61
31271950 2019
43
Spinocerebellar Ataxia Type 28-Phenotypic and Molecular Characterization of a Family with Heterozygous and Compound-Heterozygous Mutations in AFG3L2. 61
31111429 2019
44
ARSACS as a Worldwide Disease: Novel SACS Mutations Identified in a Consanguineous Family from the Remote Tribal Jammu and Kashmir Region in India. 61
30963395 2019
45
Astrocyte-specific deletion of the mitochondrial m-AAA protease reveals glial contribution to neurodegeneration. 61
30989755 2019
46
Functional Transcriptome Analysis in ARSACS KO Cell Model Reveals a Role of Sacsin in Autophagy. 61
31417125 2019
47
Paclitaxel-Promoted Supramolecular Polymerization of Peptide Conjugates. 61
31251590 2019
48
Bioinformatics-Based Identification of Expanded Repeats: A Non-reference Intronic Pentamer Expansion in RFC1 Causes CANVAS. 61
31230722 2019
49
Subtle Imaging Findings Aid the Diagnosis of Adolescent Hereditary Spastic Paraplegia and Ataxia. 61
29379980 2019
50
SYNE1-ataxia: Novel genotypic and phenotypic findings. 61
30573412 2019

Variations for Spastic Ataxia

ClinVar genetic disease variations for Spastic Ataxia:

6 ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 HARS1 NM_002109.6(HARS1):c.616G>T (p.Asp206Tyr)SNV Pathogenic 804285 5:140057507-140057507 5:140677922-140677922
2 HARS1 NM_002109.6:c.730delGdeletion Pathogenic 804286
3 INCA1 , KIF1C NM_006612.6(KIF1C):c.864+1G>ASNV Likely pathogenic 560374 rs1567721108 17:4907212-4907212 17:5003917-5003917
4 SPG7 NM_003119.4(SPG7):c.1990_1992del (p.Gln664del)deletion Likely pathogenic 625204 16:89620253-89620255 16:89553845-89553847
5 SPG7 NM_003119.4(SPG7):c.1529C>T (p.Ala510Val)SNV Conflicting interpretations of pathogenicity 42016 rs61755320 16:89613145-89613145 16:89546737-89546737
6 KCNMA1 NM_001161352.2(KCNMA1):c.1361C>A (p.Ala454Asp)SNV Uncertain significance 373984 rs1057518815 10:78846325-78846325 10:77086567-77086567
7 CACNA1A NM_000068.4(CACNA1A):c.5015G>A (p.Arg1672Gln)SNV Uncertain significance 585575 rs1568447650 19:13346498-13346498 19:13235684-13235684

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 9.5 SPG7 MTPAP MARS2 KIF1C KIF1A HARS1
2 nucleotide binding GO:0000166 9.23 TUBB2A SPG7 MTPAP MARS2 KIF1C KIF1A
3 ATP-dependent microtubule motor activity, plus-end-directed GO:0008574 9.16 KIF1C KIF1A

Sources for Spastic Ataxia

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
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
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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