Autosomal recessive spastic paraplegia type 46

General Information (adopted from Orphanet):

Synonyms, Signs: SPG46
Number of Symptoms 48
OrphanetNr: 320391
OMIM Id: 614409
ICD-10: G11.4
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: No data available.
Inheritance: Autosomal recessive
23332916 [IBIS]
Age of onset: Infancy
Childhood
23332916; 23332917 [IBIS]

Disease classification (adopted from Orphanet):

Parent Diseases: Autosomal recessive complex spastic paraplegia
 -Rare genetic disease
 -Rare neurologic disease

Comment:

Spastic paraplegia 46 (SPG46) refers to a locus mapped to chromosome 9 that accounts for a complicated autosomal-recessive form of hereditary spastic paraplegia (HSP). The loss of function of glucocerebrosidase GBA2 is responsible for the typical motor neuron defects in HSP. GBA2 encodes a microsomal nonlysosomal glucosylceramidase that catalyzes the conversion of glucosylceramide to free glucose and ceramide and the hydrolysis of bile acid 3-O-glucosides (PMID:23332916).

Symptom Information: Sort by abundance 

1
(HPO:0000518) Cataract 23332916 IBIS 454 / 7739
2
(HPO:0000519) Congenital cataract 23332916 IBIS 73 / 7739
3
(HPO:0008003) Jerky ocular pursuit movements 23332917 IBIS 4 / 7739
4
(HPO:0000639) Nystagmus 23332917 IBIS 555 / 7739
5
(HPO:0000486) Strabismus 20593214 IBIS 576 / 7739
6
(HPO:0011448) Ankle clonus 23332917 IBIS 31 / 7739
7
(HPO:0011449) Knee clonus 23332917 IBIS 10 / 7739
8
(HPO:0003690) Limb muscle weakness 23332916 IBIS 41 / 7739
9
(HPO:0007340) Lower limb muscle weakness 23332916 IBIS 61 / 7739
10
(HPO:0007002) Motor axonal neuropathy 23332916 IBIS 17 / 7739
11
(HPO:0007178) Motor polyneuropathy 20593214 IBIS 31 / 7739
12
(HPO:0002495) Impaired vibratory sensation 23332917 IBIS 26 / 7739
13
(HPO:0007133) Progressive peripheral neuropathy 20593214 IBIS 4 / 7739
14
(HPO:0002200) Pseudobulbar signs 20593214 IBIS 15 / 7739
15
(HPO:0007256) Abnormal pyramidal signs 23332916 IBIS 116 / 7739
16
(HPO:0003487) Babinski sign 23332917 IBIS 179 / 7739
17
(HPO:0001347) Hyperreflexia 23332917 IBIS 363 / 7739
18
(HPO:0001348) Brisk reflexes 23332916 IBIS 15 / 7739
19
(HPO:0001276) Hypertonia 23332917 IBIS 317 / 7739
20
(HPO:0002061) Lower limb spasticity 23332916 IBIS 56 / 7739
21
(HPO:0001258) Spastic paraplegia 23332916 IBIS 97 / 7739
22
(HPO:0002064) Spastic gait 23332916 IBIS 46 / 7739
23
(HPO:0006986) Upper limb spasticity 23332917 IBIS 15 / 7739
24
(HPO:0002493) Upper motor neuron dysfunction 23332916 IBIS 5 / 7739
25
(HPO:0001251) Ataxia 23332916 IBIS 413 / 7739
26
(HPO:0002311) Incoordination 23332917 IBIS 84 / 7739
27
(HPO:0001260) Dysarthria 23332917 IBIS 329 / 7739
28
(HPO:0000726) Dementia rare [HPO:skoehler] 23332916 IBIS 131 / 7739
29
(HPO:0001268) Mental deterioration 23332916 IBIS 88 / 7739
30
(HPO:0100543) Cognitive impairment 23332916 IBIS 230 / 7739
31
(HPO:0001288) Gait disturbance 20593214 IBIS 318 / 7739
32
(HPO:0002346) Head tremor rare [HPO:skoehler] 23332917 IBIS 9 / 7739
33
(HPO:0001250) Seizures 20593214 IBIS 1245 / 7739
34
(HPO:0001761) Pes cavus 23332917 IBIS 225 / 7739
35
(HPO:0002650) Scoliosis rare [HPO:skoehler] 23332917 IBIS 705 / 7739
36
(HPO:0002079) Hypoplasia of the corpus callosum 20593214 IBIS 161 / 7739
37
(HPO:0002240) Hepatomegaly 23332917 IBIS 467 / 7739
38
(HPO:0000026) Male hypogonadism 23332916 IBIS 20 / 7739
39
(HPO:0008734) Decreased testicular size 23332916 IBIS 105 / 7739
40
(HPO:0000789) Infertility rare [HPO:skoehler] 23332916 IBIS 74 / 7739
41
(HPO:0002839) Urinary bladder sphincter dysfunction 23332917 IBIS 34 / 7739
42
(HPO:0000365) Hearing impairment rare [HPO:skoehler] 23332916 IBIS 539 / 7739
43
(HPO:0001272) Cerebellar atrophy 23332916 IBIS 197 / 7739
44
(HPO:0002059) Cerebral atrophy 23332916 IBIS 171 / 7739
45
(HPO:0007371) Corpus callosum atrophy 23332916 IBIS 14 / 7739
46
(HPO:0003676) Progressive disorder 23332916 IBIS 148 / 7739
47
(HPO:0003677) Slow progression 23332916 IBIS 134 / 7739
48
(OMIM) Abnormal sperm head (in some patients) 23332916 IBIS 1 / 7739

Associated genes:

GBA2;

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) 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 ...
Clinical Description OMIM Boukhris et al. (2008) reported a consanguineous Tunisian family (TUN35) in which 5 individuals had a form of early-onset complicated spastic paraplegia. The patients had insidious onset of stiffness and weakness of the lower limbs between 2 and ...
Molecular genetics OMIM In 11 patients from 4 unrelated families with autosomal recessive hereditary spastic paraplegia-46, Martin et al. (2013) identified 4 different biallelic mutations in the GBA2 gene (609471.0001-609471.0004). Three of the mutations were truncating, and 1 was a missense ...