SPAX5
MCID: SPS212
MIFTS: 26

Spastic Ataxia 5, Autosomal Recessive (SPAX5)

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

Aliases & Classifications for Spastic Ataxia 5, Autosomal Recessive

MalaCards integrated aliases for Spastic Ataxia 5, Autosomal Recessive:

Name: Spastic Ataxia 5, Autosomal Recessive 56 73 29 6 71
Spax5 56 58 73
Afg3l2-Related Spastic Ataxia-Myoclonic Epilepsy-Neuropathy Syndrome 58
Early-Onset Spastic Ataxia-Myoclonic Epilepsy-Neuropathy Syndrome 58
Ataxia, Spastic, Type 5, Autosomal Recessive 39
Autosomal Recessive Spastic Ataxia Type 5 58
Ataxia, Spastic, 5, Autosomal Recessive 13

Characteristics:

Orphanet epidemiological data:

58
early-onset spastic ataxia-myoclonic epilepsy-neuropathy syndrome
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood;

OMIM:

56
Inheritance:
autosomal recessive

Miscellaneous:
variable severity
progressive disorder
onset in infancy or early childhood
not all patients have all features
four patients from 3 families have been reported (last curated january 2015)


HPO:

31
spastic ataxia 5, autosomal recessive:
Inheritance autosomal recessive inheritance
Onset and clinical course variable expressivity infantile onset progressive


Classifications:

Orphanet: 58  
Rare neurological diseases
Inborn errors of metabolism


Summaries for Spastic Ataxia 5, Autosomal Recessive

OMIM : 56 Spastic ataxia-5 (SPAX5) is an autosomal recessive neurodegenerative disorder characterized by early-onset spasticity resulting in significantly impaired ambulation, cerebellar ataxia, oculomotor apraxia, dystonia, and myoclonic epilepsy (summary by Pierson et al., 2011). For a discussion of genetic heterogeneity of spastic ataxia, see SPAX1 (108600). (614487)

MalaCards based summary : Spastic Ataxia 5, Autosomal Recessive, is also known as spax5, and has symptoms including ataxia, myoclonus and dysdiadochokinesis. An important gene associated with Spastic Ataxia 5, Autosomal Recessive is AFG3L2 (AFG3 Like Matrix AAA Peptidase Subunit 2). Affiliated tissues include skeletal muscle and eye, and related phenotypes are eeg abnormality and ptosis

UniProtKB/Swiss-Prot : 73 Spastic ataxia 5, autosomal recessive: A neurodegenerative disorder characterized by early onset spasticity, peripheral neuropathy, ptosis, oculomotor apraxia, dystonia, cerebellar atrophy, and progressive myoclonic epilepsy.

Related Diseases for Spastic Ataxia 5, Autosomal Recessive

Symptoms & Phenotypes for Spastic Ataxia 5, Autosomal Recessive

Human phenotypes related to Spastic Ataxia 5, Autosomal Recessive:

58 31 (show all 30)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 eeg abnormality 58 31 frequent (33%) Frequent (79-30%) HP:0002353
2 ptosis 58 31 frequent (33%) Frequent (79-30%) HP:0000508
3 dysphagia 58 31 frequent (33%) Frequent (79-30%) HP:0002015
4 myoclonus 58 31 frequent (33%) Frequent (79-30%) HP:0001336
5 intellectual disability, mild 58 31 frequent (33%) Frequent (79-30%) HP:0001256
6 generalized myoclonic seizures 58 31 frequent (33%) Frequent (79-30%) HP:0002123
7 dysmetria 58 31 frequent (33%) Frequent (79-30%) HP:0001310
8 dystonia 58 31 frequent (33%) Frequent (79-30%) HP:0001332
9 generalized tonic-clonic seizures 58 31 frequent (33%) Frequent (79-30%) HP:0002069
10 cerebellar hypoplasia 58 31 frequent (33%) Frequent (79-30%) HP:0001321
11 dysdiadochokinesis 58 31 frequent (33%) Frequent (79-30%) HP:0002075
12 abnormal mitochondria in muscle tissue 58 31 frequent (33%) Frequent (79-30%) HP:0008316
13 cerebellar atrophy 58 31 frequent (33%) Frequent (79-30%) HP:0001272
14 sensorimotor neuropathy 58 31 frequent (33%) Frequent (79-30%) HP:0007141
15 distal amyotrophy 58 31 frequent (33%) Frequent (79-30%) HP:0003693
16 lower limb muscle weakness 58 31 frequent (33%) Frequent (79-30%) HP:0007340
17 oculomotor apraxia 58 31 frequent (33%) Frequent (79-30%) HP:0000657
18 peripheral axonal neuropathy 58 31 frequent (33%) Frequent (79-30%) HP:0003477
19 distal muscle weakness 58 31 frequent (33%) Frequent (79-30%) HP:0002460
20 spastic paraparesis 58 31 frequent (33%) Frequent (79-30%) HP:0002313
21 demyelinating peripheral neuropathy 58 31 frequent (33%) Frequent (79-30%) HP:0007108
22 spastic dysarthria 58 31 frequent (33%) Frequent (79-30%) HP:0002464
23 cognitive impairment 31 occasional (7.5%) HP:0100543
24 spasticity 58 Frequent (79-30%)
25 ataxia 58 Frequent (79-30%)
26 dysarthria 31 HP:0001260
27 muscle weakness 31 HP:0001324
28 skeletal muscle atrophy 31 HP:0003202
29 increased intramyocellular lipid droplets 31 HP:0012240
30 spastic ataxia 31 HP:0002497

Symptoms via clinical synopsis from OMIM:

56
Neurologic Central Nervous System:
spasticity
ataxia
dysarthria
myoclonus
dysmetria
more
Abdomen Gastrointestinal:
dysphagia

Neurologic Peripheral Nervous System:
axonal peripheral sensorimotor neuropathy
chronic demyelinating/remyelinating process seen on sural nerve biopsy

Head And Neck Eyes:
ptosis
oculomotor apraxia

Muscle Soft Tissue:
distal muscle atrophy, affecting the lower limbs
distal muscle weakness, affecting the lower limbs
misplaced mitochondria seen on skeletal muscle biopsy
large lipid droplets
decreased mtdna

Clinical features from OMIM:

614487

UMLS symptoms related to Spastic Ataxia 5, Autosomal Recessive:


ataxia, myoclonus, dysdiadochokinesis, muscle spasticity, myoclonic seizures, paraparesis, spastic

Drugs & Therapeutics for Spastic Ataxia 5, Autosomal Recessive

Search Clinical Trials , NIH Clinical Center for Spastic Ataxia 5, Autosomal Recessive

Genetic Tests for Spastic Ataxia 5, Autosomal Recessive

Genetic tests related to Spastic Ataxia 5, Autosomal Recessive:

# Genetic test Affiliating Genes
1 Spastic Ataxia 5, Autosomal Recessive 29 AFG3L2

Anatomical Context for Spastic Ataxia 5, Autosomal Recessive

MalaCards organs/tissues related to Spastic Ataxia 5, Autosomal Recessive:

40
Skeletal Muscle, Eye

Publications for Spastic Ataxia 5, Autosomal Recessive

Articles related to Spastic Ataxia 5, Autosomal Recessive:

# Title Authors PMID Year
1
A recurrent de novo mutation in KCNC1 causes progressive myoclonus epilepsy. 56 6
25401298 2015
2
Whole-exome sequencing identifies homozygous AFG3L2 mutations in a spastic ataxia-neuropathy syndrome linked to mitochondrial m-AAA proteases. 56 6
22022284 2011
3
Pathogenic variants in the AFG3L2 proteolytic domain cause SCA28 through haploinsufficiency and proteostatic stress-driven OMA1 activation. 61
30910913 2019
4
Spinocerebellar Ataxia Type 28-Phenotypic and Molecular Characterization of a Family with Heterozygous and Compound-Heterozygous Mutations in AFG3L2. 61
31111429 2019

Variations for Spastic Ataxia 5, Autosomal Recessive

ClinVar genetic disease variations for Spastic Ataxia 5, Autosomal Recessive:

6 ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 AFG3L2 NM_006796.2(AFG3L2):c.1875G>A (p.Met625Ile)SNV Pathogenic 162524 rs727502823 18:12340305-12340305 18:12340306-12340306
2 AFG3L2 NM_006796.2(AFG3L2):c.1847A>G (p.Tyr616Cys)SNV Likely pathogenic 30427 rs387906889 18:12340333-12340333 18:12340334-12340334
3 AFG3L2 NM_006796.2(AFG3L2):c.1951A>G (p.Arg651Gly)SNV Likely pathogenic 374935 rs764254189 18:12340229-12340229 18:12340230-12340230
4 AFG3L2 NM_006796.2(AFG3L2):c.571G>A (p.Val191Ile)SNV Uncertain significance 548568 rs1373473541 18:12363837-12363837 18:12363838-12363838
5 AFG3L2 NM_006796.2(AFG3L2):c.1397C>T (p.Pro466Leu)SNV Uncertain significance 214053 rs375098002 18:12351334-12351334 18:12351335-12351335

UniProtKB/Swiss-Prot genetic disease variations for Spastic Ataxia 5, Autosomal Recessive:

73
# Symbol AA change Variation ID SNP ID
1 AFG3L2 p.Tyr616Cys VAR_067330 rs387906889

Expression for Spastic Ataxia 5, Autosomal Recessive

Search GEO for disease gene expression data for Spastic Ataxia 5, Autosomal Recessive.

Pathways for Spastic Ataxia 5, Autosomal Recessive

GO Terms for Spastic Ataxia 5, Autosomal Recessive

Sources for Spastic Ataxia 5, Autosomal Recessive

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HMDB
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32 ICD10
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44 MESH via Orphanet
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48 NCI
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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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