Autosomal recessive spastic paraplegia type 46
Synonyms: SPG46
- Type
- Disease
- Group
- Disorder
- Inheritance
- Autosomal recessive
- Age of onset
- Childhood, Infancy
- Status
- active
Autosomal recessive spastic paraplegia type 46 (SPG46) is a rare, complex type of hereditary spastic paraplegia characterized by an onset, in infancy or childhood, of the typical signs of spastic paraplegia (i.e. spastic gait and weakness of the lower limbs) associated with a variety of additional manifestations including upper limb spasticity and weakness, pseudobulbar dysarthria, bladder dysfunction, cerebellar ataxia, cataracts, and cognitive impairment that can progress to dementia. Brain imaging may show thinning of the corpus callosum and mild atrophy of the cerebrum and cerebellum. SPG46 is due to mutations in the <i>GBA2</i> gene (9p13.2) encoding non-lysosomal glucosylceramidase.
Names in Orphadata languages
12 of 12 languages| Lang | Name | Synonyms |
|---|---|---|
| en | Autosomal recessive spastic paraplegia type 46 | SPG46 |
| fr | Paraplégie spastique autosomique récessive type 46 | = en |
| de | Spastische Paraplegie, autosomal-rezessive, Typ 46 | = en |
| es | Paraparesia espástica autosómica recesiva tipo 46 | SPG46 · Paraplejía espástica autosómica recesiva tipo 46 |
| it | Paraplegia spastica autosomica recessiva, tipo 46 | = en |
| nl | Autosomaal recessieve spastische paraplegie type 46 | = en |
| pt | Paraplegia espástica autossómica recessiva tipo 46 | |
| pl | Autosomalna recesywna paraplegia spastyczna typu 46 | = en |
| cs | Autozomálně recesivní spastická paraplegie, typ 46 | = en |
| uk | Аутосомно-рецесивна спастична параплегія, тип 46 | = en |
| zh | 常染色体隐性遗传痉挛性截瘫46型 | = en |
| tr | Otozomal resesif spastik parapleji tip 46 | = en |
Definition in:
Cross-references
qualifier = Orphanet mapping relation| Source | Code | Qualifier | ICD relation | Validation |
|---|---|---|---|---|
| OMIM | 614409 | E | validated | |
| ICD-10 | G11.4 | NTBT | attributed | validated |
| ICD-11 | 8B44.01 | NTBT | attributed | validated |
| MONDO | 0013737 | E | validated | |
| UMLS | C2828721 | E | validated | |
| GARD | 17476 | E | validated |
E exact · NTBT this ORPHAcode is narrower than the target · BTNT broader than the target · ND not decided.
Classification
Preferential parent (Orphanet linearisation):
Parents in the classifications (2):
- ORPHA:100981Autosomal recessive complex spastic paraplegia
rare genetic diseases; rare neurological diseases - ORPHA:611314Rare syndromic intellectual disability without multiple congenital anomalies/dysmorphic syndrome
rare genetic diseases; rare neurological diseases
No children.
Genes
1 direct| Gene | Association | Status | HGNC | Ensembl | OMIM | Locus | Name | Source of validation |
|---|---|---|---|---|---|---|---|---|
| GBA2 | Disease-causing germline mutation(s) (loss of function) in | Assessed | HGNC:18986 | ENSG00000070610 | 609471 | 9p13.3 | glucosylceramidase beta 2 | 23332916[PMID] |
Prevalence and incidence
2 records| Type | Class | Value | Area | Qualification | Validation | Source |
|---|---|---|---|---|---|---|
| Cases/families | 5 cases | Worldwide | Case(s) | Validated | 20593214[PMID] | |
| Point prevalence | <1 / 1 000 000 | — | Worldwide | Class only | Validated | ORPHANET_20593214[PMID] |
Value is Orphadata's ValMoy: the mean estimate per 100 000 for prevalence and incidence, the number of cases or families for case reports.
HPO phenotypes
33 annotations · validated 2018-04-05| HPO | Term (as annotated by Orphanet) | Diagnostic |
|---|---|---|
| Very frequent (99-80%) | ||
| HP:0001251 | Ataxia | |
| HP:0003487 | Babinski sign | |
| HP:0000518 | Cataract | |
| HP:0001288 | Gait disturbance | |
| HP:0002061 | Lower limb spasticity | |
| Frequent (79-30%) | ||
| HP:0002500 | Abnormal cerebral white matter morphology | |
| HP:0001272 | Cerebellar atrophy | |
| HP:0002059 | Cerebral atrophy | |
| HP:0002120 | Cerebral cortical atrophy | |
| HP:0100543 | Cognitive impairment | |
| HP:0007371 | Corpus callosum atrophy | |
| Occasional (29-5%) | ||
| HP:0007256 | Abnormal pyramidal sign | |
| HP:0012864 | Abnormal sperm morphology | |
| HP:0100261 | Abnormal tendon morphology | |
| HP:0002136 | Broad-based gait | |
| HP:0008734 | Decreased testicular size | |
| HP:0000726 | Dementia | |
| HP:0002346 | Head tremor | |
| HP:0000365 | Hearing impairment | |
| HP:0001347 | Hyperreflexia | |
| HP:0006938 | Impaired vibration sensation at ankles | |
| HP:0000789 | Infertility | |
| HP:0008003 | Jerky ocular pursuit movements | |
| HP:0000639 | Nystagmus | |
| HP:0003477 | Peripheral axonal neuropathy | |
| HP:0001761 | Pes cavus | |
| HP:0012207 | Reduced sperm motility | |
| HP:0002650 | Scoliosis | |
| HP:0002464 | Spastic dysarthria | |
| HP:0012865 | Sperm head anomaly | |
| HP:0002078 | Truncal ataxia | |
| HP:0006986 | Upper limb spasticity | |
| HP:0000020 | Urinary incontinence | |
Run the differential on the 5 obligate / very frequent terms
Annotation source: 23332916[PMID]_23332917[PMID]_24252062[PMID]
Sources for this card
- Orphanet page: orpha.net/en/disease/detail/320391
- This record as JSON: /data/d/320391.json