SPAX5
MCID: SPS212
MIFTS: 31

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 57 72 29 6 70
Spax5 57 58 72
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®:

57 (Updated 05-Apr-2021)
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® : 57 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) (Updated 05-Apr-2021)

MalaCards based summary : Spastic Ataxia 5, Autosomal Recessive, also known as spax5, is related to spastic ataxia and ataxia and polyneuropathy, adult-onset, 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 related phenotypes are eeg abnormality and ptosis

UniProtKB/Swiss-Prot : 72 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

Graphical network of the top 20 diseases related to Spastic Ataxia 5, Autosomal Recessive:



Diseases related to 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 32)
# 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 intellectual disability, mild 58 31 frequent (33%) Frequent (79-30%) HP:0001256
5 myoclonus 58 31 frequent (33%) Frequent (79-30%) HP:0001336
6 dysmetria 58 31 frequent (33%) Frequent (79-30%) HP:0001310
7 dystonia 58 31 frequent (33%) Frequent (79-30%) HP:0001332
8 dysdiadochokinesis 58 31 frequent (33%) Frequent (79-30%) HP:0002075
9 cerebellar hypoplasia 58 31 frequent (33%) Frequent (79-30%) HP:0001321
10 abnormal mitochondria in muscle tissue 58 31 frequent (33%) Frequent (79-30%) HP:0008316
11 cerebellar atrophy 58 31 frequent (33%) Frequent (79-30%) HP:0001272
12 spastic paraparesis 58 31 frequent (33%) Frequent (79-30%) HP:0002313
13 oculomotor apraxia 58 31 frequent (33%) Frequent (79-30%) HP:0000657
14 distal muscle weakness 58 31 frequent (33%) Frequent (79-30%) HP:0002460
15 demyelinating peripheral neuropathy 58 31 frequent (33%) Frequent (79-30%) HP:0007108
16 distal amyotrophy 58 31 frequent (33%) Frequent (79-30%) HP:0003693
17 peripheral axonal neuropathy 58 31 frequent (33%) Frequent (79-30%) HP:0003477
18 sensorimotor neuropathy 58 31 frequent (33%) Frequent (79-30%) HP:0007141
19 spastic dysarthria 58 31 frequent (33%) Frequent (79-30%) HP:0002464
20 lower limb muscle weakness 58 31 frequent (33%) Frequent (79-30%) HP:0007340
21 bilateral tonic-clonic seizure 31 frequent (33%) HP:0002069
22 generalized myoclonic seizure 31 frequent (33%) HP:0002123
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 generalized myoclonic seizures 58 Frequent (79-30%)
30 generalized tonic-clonic seizures 58 Frequent (79-30%)
31 spastic ataxia 31 HP:0002497
32 increased intramyocellular lipid droplets 31 HP:0012240

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
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
optic atrophy (in some patients)

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 (Updated 05-Apr-2021)

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

Publications for Spastic Ataxia 5, Autosomal Recessive

Articles related to Spastic Ataxia 5, Autosomal Recessive:

# Title Authors PMID Year
1
ATPase Domain AFG3L2 Mutations Alter OPA1 Processing and Cause Optic Neuropathy. 57 6
32219868 2020
2
A recurrent de novo mutation in KCNC1 causes progressive myoclonus epilepsy. 57 6
25401298 2015
3
Whole-exome sequencing identifies homozygous AFG3L2 mutations in a spastic ataxia-neuropathy syndrome linked to mitochondrial m-AAA proteases. 6 57
22022284 2011
4
A novel AFG3L2 mutation close to AAA domain leads to aberrant OMA1 and OPA1 processing in a family with optic atrophy. 61
32600459 2020
5
Expanding the clinical and genetic heterogeneity of SPAX5. 61
32237276 2020
6
Pathogenic variants in the AFG3L2 proteolytic domain cause SCA28 through haploinsufficiency and proteostatic stress-driven OMA1 activation. 61
30910913 2019
7
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 (show all 14)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 AFG3L2 NM_006796.2(AFG3L2):c.1875G>A (p.Met625Ile) SNV Pathogenic 162524 rs727502823 GRCh37: 18:12340305-12340305
GRCh38: 18:12340306-12340306
2 AFG3L2 NM_006796.3(AFG3L2):c.1901_1902del (p.Val633_Ser634insTer) Microsatellite Pathogenic 973201 GRCh37: 18:12340278-12340279
GRCh38: 18:12340279-12340280
3 AFG3L2 NM_006796.3(AFG3L2):c.916A>G (p.Lys306Glu) SNV Pathogenic 973204 GRCh37: 18:12358779-12358779
GRCh38: 18:12358780-12358780
4 AFG3L2 NM_006796.2(AFG3L2):c.1847A>G (p.Tyr616Cys) SNV Pathogenic 30427 rs387906889 GRCh37: 18:12340333-12340333
GRCh38: 18:12340334-12340334
5 AFG3L2 NM_006796.3(AFG3L2):c.1858C>A (p.Gln620Lys) SNV Pathogenic 973202 GRCh37: 18:12340322-12340322
GRCh38: 18:12340323-12340323
6 AFG3L2 NM_006796.3(AFG3L2):c.1385C>T SNV Pathogenic 546814 rs912546325 GRCh37: 18:12351346-12351346
GRCh38: 18:12351347-12351347
7 AFG3L2 NM_006796.3(AFG3L2):c.1779+1G>A SNV Pathogenic 1032493 GRCh37: 18:12344130-12344130
GRCh38: 18:12344131-12344131
8 AFG3L2 NM_006796.2(AFG3L2):c.1951A>G (p.Arg651Gly) SNV Likely pathogenic 374935 rs764254189 GRCh37: 18:12340229-12340229
GRCh38: 18:12340230-12340230
9 AFG3L2 NM_006796.2(AFG3L2):c.1397C>T (p.Pro466Leu) SNV Uncertain significance 214053 rs375098002 GRCh37: 18:12351334-12351334
GRCh38: 18:12351335-12351335
10 AFG3L2 NM_006796.2(AFG3L2):c.571G>A (p.Val191Ile) SNV Uncertain significance 548568 rs1373473541 GRCh37: 18:12363837-12363837
GRCh38: 18:12363838-12363838
11 AFG3L2 , TUBB6 NM_006796.2(AFG3L2):c.2314C>T (p.Leu772Phe) SNV Uncertain significance 214057 rs117182113 GRCh37: 18:12329644-12329644
GRCh38: 18:12329645-12329645
12 AFG3L2 NM_006796.3(AFG3L2):c.1501G>A (p.Glu501Lys) SNV Uncertain significance 1030157 GRCh37: 18:12351135-12351135
GRCh38: 18:12351136-12351136
13 AFG3L2 NM_006796.3(AFG3L2):c.7C>T (p.His3Tyr) SNV Uncertain significance 1032494 GRCh37: 18:12377075-12377075
GRCh38: 18:12377076-12377076
14 AFG3L2 NM_006796.2(AFG3L2):c.838C>T (p.Arg280Trp) SNV Uncertain significance 446813 rs180989155 GRCh37: 18:12358857-12358857
GRCh38: 18:12358858-12358858

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

72
# 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
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31 HPO
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45 MESH via Orphanet
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56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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