MCID: SPS109
MIFTS: 37

Spastic Paraplegia 46, Autosomal Recessive

Categories: Genetic diseases, Neuronal diseases, Rare diseases, Eye diseases, Gastrointestinal diseases, Bone diseases, Mental diseases, Metabolic diseases

Aliases & Classifications for Spastic Paraplegia 46, Autosomal Recessive

MalaCards integrated aliases for Spastic Paraplegia 46, Autosomal Recessive:

Name: Spastic Paraplegia 46, Autosomal Recessive 57 75 29 13 6 73
Spg46 57 12 59 75
Autosomal Recessive Spastic Paraplegia Type 46 12 59
Hereditary Spastic Paraplegia 46 12 15
Paraplegia, Spastic, Type 46, Autosomal Recessive 40
Autosomal Recessive Spastic Paraplegia 46 12

Characteristics:

Orphanet epidemiological data:

59
autosomal recessive spastic paraplegia type 46
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood;

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
progressive disorder
onset in childhood (range 2 to 16 years)
some patients present with spasticity, whereas others present with cerebellar ataxia
some patients may have normal brain imaging


HPO:

32
spastic paraplegia 46, autosomal recessive:
Onset and clinical course slow progression progressive
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 59  
Rare neurological diseases


Summaries for Spastic Paraplegia 46, Autosomal Recessive

OMIM : 57 Autosomal recessive spastic paraplegia-46 (SPG46) is a neurodegenerative disorder characterized by onset in childhood of slowly progressive spastic paraplegia and cerebellar signs. Some patients have cognitive impairment, cataracts, and cerebral, cerebellar, and corpus callosum atrophy on brain imaging (summary by Boukhris et al., 2010 and Martin et al., 2013). (614409)

MalaCards based summary : Spastic Paraplegia 46, Autosomal Recessive, also known as spg46, is related to hereditary spastic paraplegia and paraplegia, and has symptoms including cerebellar ataxia and abnormal pyramidal signs. An important gene associated with Spastic Paraplegia 46, Autosomal Recessive is GBA2 (Glucosylceramidase Beta 2). Affiliated tissues include brain, and related phenotypes are nystagmus and hyperreflexia

Disease Ontology : 12 A hereditary spastic paraplegia that has material basis in mutation in the GBA2 gene on chromosome 9p.

UniProtKB/Swiss-Prot : 75 Spastic paraplegia 46, autosomal recessive: A neurodegenerative disorder characterized by onset in childhood of slowly progressive spastic paraplegia and cerebellar signs. Some patients have cognitive impairment, cataracts, and cerebral, cerebellar, and corpus callosum atrophy on brain imaging.

Related Diseases for Spastic Paraplegia 46, Autosomal Recessive

Diseases in the Spastic Paraplegia 3a family:

Spastic Paraplegia 3, Autosomal Dominant Spastic Paraplegia 4, Autosomal Dominant
Spastic Paraplegia 17, Autosomal Dominant Spastic Paraplegia 15, Autosomal Recessive
Spastic Paraplegia 23 Spastic Paraplegia 5a, Autosomal Recessive
Spastic Paraplegia 20, Autosomal Recessive Spastic Paraplegia 6, Autosomal Dominant
Spastic Paraplegia 9a, Autosomal Dominant Spastic Paraplegia 8, Autosomal Dominant
Spastic Paraplegia 10, Autosomal Dominant Spastic Paraplegia 11, Autosomal Recessive
Spastic Paraplegia 12, Autosomal Dominant Spastic Paraplegia 14, Autosomal Recessive
Spastic Paraplegia 13, Autosomal Dominant Spastic Paraplegia 19, Autosomal Dominant
Spastic Paraplegia 7, Autosomal Recessive Spastic Paraplegia 24, Autosomal Recessive
Spastic Paraplegia 25, Autosomal Recessive Spastic Paraplegia 27, Autosomal Recessive
Spastic Paraplegia 26, Autosomal Recessive Spastic Paraplegia 28, Autosomal Recessive
Spastic Paraplegia 29, Autosomal Dominant Spastic Paraplegia 33, Autosomal Dominant
Spastic Paraplegia 31, Autosomal Dominant Spastic Paraplegia 30, Autosomal Recessive
Spastic Paraplegia 18, Autosomal Recessive Spastic Paraplegia 32, Autosomal Recessive
Spastic Paraplegia 37, Autosomal Dominant Spastic Paraplegia 39, Autosomal Recessive
Spastic Paraplegia 35, Autosomal Recessive Spastic Paraplegia 38, Autosomal Dominant
Spastic Paraplegia 42, Autosomal Dominant Spastic Paraplegia 50, Autosomal Recessive
Spastic Paraplegia 36, Autosomal Dominant Spastic Paraplegia 45, Autosomal Recessive
Spastic Paraplegia 44, Autosomal Recessive Spastic Paraplegia 41, Autosomal Dominant
Spastic Paraplegia 48, Autosomal Recessive Spastic Paraplegia 51, Autosomal Recessive
Spastic Paraplegia 47, Autosomal Recessive Spastic Paraplegia 52, Autosomal Recessive
Spastic Paraplegia 46, Autosomal Recessive Spastic Paraplegia 53, Autosomal Recessive
Spastic Paraplegia 56, Autosomal Recessive Spastic Paraplegia 49, Autosomal Recessive
Spastic Paraplegia 54, Autosomal Recessive Spastic Paraplegia 55, Autosomal Recessive
Spastic Paraplegia 43, Autosomal Recessive Spastic Paraplegia 79, Autosomal Recessive
Spastic Paraplegia 72, Autosomal Recessive Spastic Paraplegia 57, Autosomal Recessive
Spastic Paraplegia 62, Autosomal Recessive Spastic Paraplegia 64, Autosomal Recessive
Spastic Paraplegia 61, Autosomal Recessive Spastic Paraplegia 63, Autosomal Recessive
Spastic Paraplegia 73, Autosomal Dominant Spastic Paraplegia 74, Autosomal Recessive
Spastic Paraplegia 9b, Autosomal Recessive Spastic Paraplegia 75, Autosomal Recessive
Spastic Paraplegia 76, Autosomal Recessive Spastic Paraplegia 77, Autosomal Recessive
Spastic Paraplegia 78, Autosomal Recessive Hereditary Spastic Paraplegia
Hereditary Spastic Paraplegia 51 Hereditary Spastic Paraplegia 72
Spastic Paraplegia 4 Spastic Paraplegia 8
Spastic Paraplegia 11 Spastic Paraplegia 1
Spastic Paraplegia 10 Spastic Paraplegia 12
Spastic Paraplegia 13 Spastic Paraplegia 14
Spastic Paraplegia 15 Spastic Paraplegia 16
Spastic Paraplegia 17 Spastic Paraplegia 18
Spastic Paraplegia 19 Spastic Paraplegia 24
Spastic Paraplegia 25 Spastic Paraplegia 26
Spastic Paraplegia 29 Spastic Paraplegia 3
Spastic Paraplegia 31 Spastic Paraplegia 32
Spastic Paraplegia 39 Spastic Paraplegia 51
Spastic Paraplegia 5a Spastic Paraplegia 5b
Spastic Paraplegia 6 Spastic Paraplegia 9
Autosomal Recessive Spastic Paraplegia Type 60 Autosomal Recessive Spastic Paraplegia Type 59
Autosomal Recessive Spastic Paraplegia Type 68 Autosomal Recessive Spastic Paraplegia Type 69
Autosomal Recessive Spastic Paraplegia Type 70 Autosomal Recessive Spastic Paraplegia Type 71
Autosomal Recessive Spastic Paraplegia Type 66 Autosomal Recessive Spastic Paraplegia Type 67

Diseases related to Spastic Paraplegia 46, Autosomal Recessive via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 20)
# Related Disease Score Top Affiliating Genes
1 hereditary spastic paraplegia 28.8 CYP2U1 GBA2 SPG21
2 paraplegia 10.1
3 spasticity 10.1
4 aceruloplasminemia 9.9
5 ataxia-oculomotor apraxia 3 9.9
6 spastic paraplegia 15, autosomal recessive 9.5 CYP2U1 SPG21
7 charcot-marie-tooth disease intermediate type 9.4 COX6A1 TRIM2
8 spastic paraplegia 35, autosomal recessive 9.2 CYP2U1 SPG21
9 charcot-marie-tooth disease type 2a2 8.9 COX6A1 SPG21 TRIM2
10 charcot-marie-tooth disease, axonal, type 2h 8.9 COX6A1 SPG21 TRIM2
11 charcot-marie-tooth disease, recessive intermediate d 8.9 COX6A1 SPG21 TRIM2
12 spastic paraplegia 55, autosomal recessive 8.9 COX6A1 SPG21 TRIM2
13 charcot-marie-tooth disease, axonal, type 2r 8.9 COX6A1 SPG21 TRIM2
14 charcot-marie-tooth disease, axonal, type 2b2 8.8 COX6A1 SPG21 TRIM2
15 charcot-marie-tooth disease, axonal, type 2p 8.8 COX6A1 SPG21 TRIM2
16 amyotrophic lateral sclerosis type 5 8.8 COX6A1 SPG21 TRIM2
17 charcot-marie-tooth disease, axonal, type 2b1 8.7 COX6A1 SPG21 TRIM2
18 spastic paraplegia 56, autosomal recessive 8.6 COX6A1 CYP2U1 GBA2 TRIM2
19 charcot-marie-tooth disease, axonal, type 2t 8.3 COX6A1 CYP2U1 SPG21 TRIM2
20 charcot-marie-tooth disease, axonal, type 2e 7.8 COX6A1 CYP2U1 GBA2 SPG21 TRIM2

Graphical network of the top 20 diseases related to Spastic Paraplegia 46, Autosomal Recessive:



Diseases related to Spastic Paraplegia 46, Autosomal Recessive

Symptoms & Phenotypes for Spastic Paraplegia 46, Autosomal Recessive

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Eyes:
nystagmus
jerky smooth pursuit
cataracts, congenital (in some patients)

Muscle Soft Tissue:
limb muscle weakness
increased muscle tone

Head And Neck Ears:
hearing loss (in some patients)

GenitourinaryInternal GenitaliaMale:
small testicles (in some patients)
abnormal sperm head (in some patients)
low sperm velocity (in some patients)
infertility (in some male patients)

Neurologic Peripheral Nervous System:
decreased vibratory sense in the lower limbs (in some patients)
axonal sensory polyneuropathy (in some patients)

Neurologic Central Nervous System:
dysarthria
hyperreflexia
cerebellar atrophy
lower limb spasticity
spastic gait
more
Skeletal Spine:
scoliosis (in some patients)
kyphosis (in some patients)

Skeletal Feet:
pes cavus (in some patients)

Genitourinary Bladder:
urinary incontinence (variable)


Clinical features from OMIM:

614409

Human phenotypes related to Spastic Paraplegia 46, Autosomal Recessive:

59 32 (show all 44)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 nystagmus 59 32 occasional (7.5%) Occasional (29-5%) HP:0000639
2 hyperreflexia 59 32 occasional (7.5%) Occasional (29-5%) HP:0001347
3 scoliosis 59 32 occasional (7.5%) Occasional (29-5%) HP:0002650
4 hearing impairment 59 32 occasional (7.5%) Occasional (29-5%) HP:0000365
5 cataract 59 32 hallmark (90%) Very frequent (99-80%) HP:0000518
6 babinski sign 59 32 hallmark (90%) Very frequent (99-80%) HP:0003487
7 pes cavus 59 32 occasional (7.5%) Occasional (29-5%) HP:0001761
8 cerebral cortical atrophy 59 32 frequent (33%) Frequent (79-30%) HP:0002120
9 decreased testicular size 59 32 occasional (7.5%) Occasional (29-5%) HP:0008734
10 dementia 59 32 occasional (7.5%) Occasional (29-5%) HP:0000726
11 abnormal tendon morphology 59 32 occasional (7.5%) Occasional (29-5%) HP:0100261
12 difficulty walking 59 32 hallmark (90%) Very frequent (99-80%) HP:0002355
13 truncal ataxia 59 32 occasional (7.5%) Occasional (29-5%) HP:0002078
14 infertility 59 32 occasional (7.5%) Occasional (29-5%) HP:0000789
15 cerebellar atrophy 59 32 frequent (33%) Frequent (79-30%) HP:0001272
16 lower limb spasticity 59 32 hallmark (90%) Very frequent (99-80%) HP:0002061
17 urinary incontinence 59 32 occasional (7.5%) Occasional (29-5%) HP:0000020
18 corpus callosum atrophy 59 32 frequent (33%) Frequent (79-30%) HP:0007371
19 head tremor 59 32 occasional (7.5%) Occasional (29-5%) HP:0002346
20 cerebral atrophy 59 32 Frequent (79-30%) HP:0002059
21 jerky ocular pursuit movements 59 32 occasional (7.5%) Occasional (29-5%) HP:0008003
22 spastic dysarthria 59 32 occasional (7.5%) Occasional (29-5%) HP:0002464
23 broad-based gait 59 32 occasional (7.5%) Occasional (29-5%) HP:0002136
24 peripheral axonal neuropathy 59 32 occasional (7.5%) Occasional (29-5%) HP:0003477
25 impaired vibration sensation at ankles 59 32 occasional (7.5%) Occasional (29-5%) HP:0006938
26 upper limb spasticity 59 32 occasional (7.5%) Occasional (29-5%) HP:0006986
27 reduced sperm motility 59 32 occasional (7.5%) Occasional (29-5%) HP:0012207
28 sperm head anomaly 59 32 occasional (7.5%) Occasional (29-5%) HP:0012865
29 intellectual disability 32 occasional (7.5%) HP:0001249
30 ataxia 59 Very frequent (99-80%)
31 dysarthria 32 HP:0001260
32 kyphosis 32 occasional (7.5%) HP:0002808
33 abnormal pyramidal signs 59 Occasional (29-5%)
34 cognitive impairment 59 Frequent (79-30%)
35 spastic paraplegia 32 HP:0001258
36 impaired vibration sensation in the lower limbs 32 occasional (7.5%) HP:0002166
37 ankle clonus 32 HP:0011448
38 spastic gait 32 HP:0002064
39 hypoplasia of the corpus callosum 32 HP:0002079
40 lower limb muscle weakness 32 HP:0007340
41 abnormality of the cerebral white matter 59 Frequent (79-30%)
42 limb dysmetria 32 HP:0002406
43 abnormal sperm morphology 59 Occasional (29-5%)
44 knee clonus 32 HP:0011449

UMLS symptoms related to Spastic Paraplegia 46, Autosomal Recessive:


cerebellar ataxia, abnormal pyramidal signs

GenomeRNAi Phenotypes related to Spastic Paraplegia 46, Autosomal Recessive according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased shRNA abundance (Z-score < -2) GR00366-A-111 9.35 GBA2
2 Decreased shRNA abundance (Z-score < -2) GR00366-A-134 9.35 COX6A1 GBA2
3 Decreased shRNA abundance (Z-score < -2) GR00366-A-145 9.35 COX6A1
4 Decreased shRNA abundance (Z-score < -2) GR00366-A-179 9.35 COX6A1
5 Mildly decreased CFP-tsO45G cell surface transport GR00360-A-1 9.02 CREB3 CYP2U1 GBA2 SPG21 TRIM2

Drugs & Therapeutics for Spastic Paraplegia 46, Autosomal Recessive

Search Clinical Trials , NIH Clinical Center for Spastic Paraplegia 46, Autosomal Recessive

Genetic Tests for Spastic Paraplegia 46, Autosomal Recessive

Genetic tests related to Spastic Paraplegia 46, Autosomal Recessive:

# Genetic test Affiliating Genes
1 Spastic Paraplegia 46, Autosomal Recessive 29 GBA2

Anatomical Context for Spastic Paraplegia 46, Autosomal Recessive

MalaCards organs/tissues related to Spastic Paraplegia 46, Autosomal Recessive:

41
Brain

Publications for Spastic Paraplegia 46, Autosomal Recessive

Variations for Spastic Paraplegia 46, Autosomal Recessive

UniProtKB/Swiss-Prot genetic disease variations for Spastic Paraplegia 46, Autosomal Recessive:

75
# Symbol AA change Variation ID SNP ID
1 GBA2 p.Arg630Trp VAR_069634 rs398123012
2 GBA2 p.Arg873His VAR_069635 rs398123015

ClinVar genetic disease variations for Spastic Paraplegia 46, Autosomal Recessive:

6
(show all 15)
# Gene Variation Type Significance SNP ID Assembly Location
1 GBA2 NM_020944.2(GBA2): c.1888C> T (p.Arg630Trp) single nucleotide variant Pathogenic rs398123012 GRCh37 Chromosome 9, 35738808: 35738808
2 GBA2 NM_020944.2(GBA2): c.1888C> T (p.Arg630Trp) single nucleotide variant Pathogenic rs398123012 GRCh38 Chromosome 9, 35738811: 35738811
3 GBA2 NM_020944.2(GBA2): c.700C> T (p.Arg234Ter) single nucleotide variant Pathogenic rs398123013 GRCh37 Chromosome 9, 35741755: 35741755
4 GBA2 NM_020944.2(GBA2): c.700C> T (p.Arg234Ter) single nucleotide variant Pathogenic rs398123013 GRCh38 Chromosome 9, 35741758: 35741758
5 GBA2 GBA2, TRP173TER undetermined variant Pathogenic
6 GBA2 GBA2, 4-BP DUP, 1471GGCA duplication Pathogenic
7 GBA2 NM_020944.2(GBA2): c.1018C> T (p.Arg340Ter) single nucleotide variant Pathogenic rs398123014 GRCh37 Chromosome 9, 35740830: 35740830
8 GBA2 NM_020944.2(GBA2): c.1018C> T (p.Arg340Ter) single nucleotide variant Pathogenic rs398123014 GRCh38 Chromosome 9, 35740833: 35740833
9 GBA2 NM_020944.2(GBA2): c.2618G> A (p.Arg873His) single nucleotide variant Pathogenic rs398123015 GRCh37 Chromosome 9, 35737332: 35737332
10 GBA2 NM_020944.2(GBA2): c.2618G> A (p.Arg873His) single nucleotide variant Pathogenic rs398123015 GRCh38 Chromosome 9, 35737335: 35737335
11 GBA2 GBA2, TYR121TER single nucleotide variant Pathogenic
12 GBA2 NM_020944.2(GBA2): c.1780G> C (p.Asp594His) single nucleotide variant Pathogenic rs398123064 GRCh37 Chromosome 9, 35739014: 35739014
13 GBA2 NM_020944.2(GBA2): c.1780G> C (p.Asp594His) single nucleotide variant Pathogenic rs398123064 GRCh38 Chromosome 9, 35739017: 35739017
14 GBA2 NM_020944.2(GBA2): c.1030G> C (p.Ala344Pro) single nucleotide variant not provided rs750984776 GRCh38 Chromosome 9, 35740625: 35740625
15 GBA2 NM_020944.2(GBA2): c.1030G> C (p.Ala344Pro) single nucleotide variant not provided rs750984776 GRCh37 Chromosome 9, 35740622: 35740622

Expression for Spastic Paraplegia 46, Autosomal Recessive

Search GEO for disease gene expression data for Spastic Paraplegia 46, Autosomal Recessive.

Pathways for Spastic Paraplegia 46, Autosomal Recessive

GO Terms for Spastic Paraplegia 46, Autosomal Recessive

Cellular components related to Spastic Paraplegia 46, Autosomal Recessive according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 endoplasmic reticulum membrane GO:0005789 8.8 CREB3 CYP2U1 GBA2

Sources for Spastic Paraplegia 46, Autosomal Recessive

3 CDC
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10 dbSNP
11 DGIdb
17 ExPASy
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34 ICD10 via Orphanet
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36 IUPHAR
37 KEGG
38 LifeMap
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44 MeSH
45 MESH via Orphanet
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58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
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74 UMLS via Orphanet
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