SPAX4
MCID: SPS208
MIFTS: 26

Spastic Ataxia 4, Autosomal Recessive (SPAX4)

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

Aliases & Classifications for Spastic Ataxia 4, Autosomal Recessive

MalaCards integrated aliases for Spastic Ataxia 4, Autosomal Recessive:

Name: Spastic Ataxia 4, Autosomal Recessive 58 54 76 74
Spax4 58 54 60 76
Autosomal Recessive Spastic Ataxia-Optic Atrophy-Dysarthria Syndrome 54 60
Autosomal Recessive Spastic Ataxia Type 4 54 60
Ataxia, Spastic, 4, Autosomal Recessive 30 6
Autosomal Recessive Spastic Ataxia - Optic Atrophy - Dysarthria 54
Autosomal Recessive Spastic Ataxia 4 54

Characteristics:

Orphanet epidemiological data:

60
autosomal recessive spastic ataxia-optic atrophy-dysarthria syndrome
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood;

OMIM:

58
Inheritance:
autosomal recessive

Miscellaneous:
slowly progressive disorder
onset in early childhood
most retain independent ambulation
one family from the old order amish has been reported (last curated january 2015)


HPO:

33
spastic ataxia 4, autosomal recessive:
Onset and clinical course slow progression
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Spastic Ataxia 4, Autosomal Recessive

NIH Rare Diseases : 54 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 254343Disease definitionA rare, genetic, autosomal recessive spastic ataxia disease characterized by onset in early childhood of spastic paraparesis, cerebellar ataxia, dysarthria and optic atrophy.Visit the Orphanet disease page for more resources.

MalaCards based summary : Spastic Ataxia 4, Autosomal Recessive, is also known as spax4, and has symptoms including paraparesis, spastic An important gene associated with Spastic Ataxia 4, Autosomal Recessive is MTPAP (Mitochondrial Poly(A) Polymerase). Affiliated tissues include tongue and eye, and related phenotypes are dysarthria and hyperreflexia

UniProtKB/Swiss-Prot : 76 Spastic ataxia 4, autosomal recessive: A slowly progressive neurodegenerative disease characterized by cerebellar ataxia, spastic paraparesis, dysarthria, and optic atrophy.

Description from OMIM: 613672

Related Diseases for Spastic Ataxia 4, Autosomal Recessive

Symptoms & Phenotypes for Spastic Ataxia 4, Autosomal Recessive

Human phenotypes related to Spastic Ataxia 4, Autosomal Recessive:

60 33 (show all 19)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 dysarthria 60 33 hallmark (90%) Very frequent (99-80%) HP:0001260
2 hyperreflexia 60 33 hallmark (90%) Very frequent (99-80%) HP:0001347
3 optic atrophy 60 33 hallmark (90%) Very frequent (99-80%) HP:0000648
4 babinski sign 60 33 hallmark (90%) Very frequent (99-80%) HP:0003487
5 spastic paraparesis 60 33 hallmark (90%) Very frequent (99-80%) HP:0002313
6 nystagmus 60 33 frequent (33%) Frequent (79-30%) HP:0000639
7 myoclonus 60 33 frequent (33%) Frequent (79-30%) HP:0001336
8 motor delay 60 33 frequent (33%) Frequent (79-30%) HP:0001270
9 progressive cerebellar ataxia 60 33 frequent (33%) Frequent (79-30%) HP:0002073
10 progressive gait ataxia 60 33 frequent (33%) Frequent (79-30%) HP:0007240
11 frequent falls 60 33 frequent (33%) Frequent (79-30%) HP:0002359
12 lower limb hypertonia 60 33 frequent (33%) Frequent (79-30%) HP:0006895
13 movement abnormality of the tongue 60 33 frequent (33%) Frequent (79-30%) HP:0000182
14 upper limb hypertonia 60 33 frequent (33%) Frequent (79-30%) HP:0200049
15 emotional lability 60 33 occasional (7.5%) Occasional (29-5%) HP:0000712
16 hyporeflexia 60 33 occasional (7.5%) Occasional (29-5%) HP:0001265
17 delayed speech and language development 33 HP:0000750
18 spastic ataxia 33 HP:0002497
19 delayed ability to walk 33 HP:0031936

Symptoms via clinical synopsis from OMIM:

58
Head And Neck Eyes:
nystagmus
optic atrophy

Head And Neck Face:
brisk jaw jerk

Neurologic Behavioral Psychiatric Manifestations:
emotional lability (in some)

Neurologic Central Nervous System:
dysarthria
spastic paraparesis
extensor plantar responses
delayed walking
learning difficulties
more
Head And Neck Mouth:
poor oromandibular coordination
slow, spastic tongue movements

Laboratory Abnormalities:
fibroblasts shows defects in oxidative phosphorylation
decreased amount and activity of mitochondrial complexes i and iv

Clinical features from OMIM:

613672

UMLS symptoms related to Spastic Ataxia 4, Autosomal Recessive:


paraparesis, spastic

Drugs & Therapeutics for Spastic Ataxia 4, Autosomal Recessive

Interventional clinical trials:


# 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 4, Autosomal Recessive

Genetic Tests for Spastic Ataxia 4, Autosomal Recessive

Genetic tests related to Spastic Ataxia 4, Autosomal Recessive:

# Genetic test Affiliating Genes
1 Ataxia, Spastic, 4, Autosomal Recessive 30 MTPAP

Anatomical Context for Spastic Ataxia 4, Autosomal Recessive

MalaCards organs/tissues related to Spastic Ataxia 4, Autosomal Recessive:

42
Tongue, Eye

Publications for Spastic Ataxia 4, Autosomal Recessive

Articles related to Spastic Ataxia 4, Autosomal Recessive:

# Title Authors Year
1
Structure of mitochondrial poly(A) RNA polymerase reveals the structural basis for dimerization, ATP selectivity and the SPAX4 disease phenotype. ( 26319014 )
2015
2
A human mitochondrial poly(A) polymerase mutation reveals the complexities of post-transcriptional mitochondrial gene expression. ( 25008111 )
2014
3
Defective mitochondrial mRNA maturation is associated with spastic ataxia. ( 20970105 )
2010

Variations for Spastic Ataxia 4, Autosomal Recessive

UniProtKB/Swiss-Prot genetic disease variations for Spastic Ataxia 4, Autosomal Recessive:

76
# Symbol AA change Variation ID SNP ID
1 MTPAP p.Asn478Asp VAR_064907 rs267606900

ClinVar genetic disease variations for Spastic Ataxia 4, Autosomal Recessive:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 MTPAP NM_018109.3(MTPAP): c.1432A> G (p.Asn478Asp) single nucleotide variant Pathogenic rs267606900 GRCh37 Chromosome 10, 30602855: 30602855
2 MTPAP NM_018109.3(MTPAP): c.1432A> G (p.Asn478Asp) single nucleotide variant Pathogenic rs267606900 GRCh38 Chromosome 10, 30313926: 30313926
3 MTPAP NM_018109.3(MTPAP): c.484C> T (p.Arg162Cys) single nucleotide variant Benign rs1047991 GRCh37 Chromosome 10, 30629226: 30629226
4 MTPAP NM_018109.3(MTPAP): c.484C> T (p.Arg162Cys) single nucleotide variant Benign rs1047991 GRCh38 Chromosome 10, 30340297: 30340297
5 MTPAP NM_018109.3(MTPAP): c.555+19C> T single nucleotide variant Benign rs1047988 GRCh37 Chromosome 10, 30629136: 30629136
6 MTPAP NM_018109.3(MTPAP): c.555+19C> T single nucleotide variant Benign rs1047988 GRCh38 Chromosome 10, 30340207: 30340207
7 MTPAP NM_018109.3(MTPAP): c.1468G> T (p.Val490Leu) single nucleotide variant Uncertain significance rs1057518710 GRCh37 Chromosome 10, 30602819: 30602819
8 MTPAP NM_018109.3(MTPAP): c.1468G> T (p.Val490Leu) single nucleotide variant Uncertain significance rs1057518710 GRCh38 Chromosome 10, 30313890: 30313890
9 MTPAP NM_018109.3(MTPAP): c.346G> A (p.Val116Ile) single nucleotide variant Uncertain significance rs560622337 GRCh37 Chromosome 10, 30629364: 30629364
10 MTPAP NM_018109.3(MTPAP): c.346G> A (p.Val116Ile) single nucleotide variant Uncertain significance rs560622337 GRCh38 Chromosome 10, 30340435: 30340435

Expression for Spastic Ataxia 4, Autosomal Recessive

Search GEO for disease gene expression data for Spastic Ataxia 4, Autosomal Recessive.

Pathways for Spastic Ataxia 4, Autosomal Recessive

GO Terms for Spastic Ataxia 4, Autosomal Recessive

Sources for Spastic Ataxia 4, Autosomal Recessive

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
20 FMA
29 GO
30 GTR
31 HGMD
32 HMDB
33 HPO
34 ICD10
35 ICD10 via Orphanet
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37 IUPHAR
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45 MeSH
46 MESH via Orphanet
47 MGI
50 NCI
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52 NDF-RT
55 NINDS
56 Novoseek
58 OMIM
59 OMIM via Orphanet
63 PubMed
65 QIAGEN
70 SNOMED-CT via HPO
71 SNOMED-CT via Orphanet
72 TGDB
73 Tocris
74 UMLS
75 UMLS via Orphanet
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