hereditary spastic paraplegia 46
Findings
No curated finding names hereditary spastic paraplegia 46 yet. Everything below is reference data from Mondo, HPO and GenCC, not evidence about what affects it.
Definition
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 GBA2 gene (9p13.2) encoding non-lysosomal glucosylceramidase.
Definition from the Mondo Disease Ontology (MONDO:0013737), read 2026-09-29. CC BY 4.0.
- Inheritance
- Autosomal recessive inheritance
- Onset and course
- Juvenile onset · Progressive · Childhood onset
HPO, annotations 2026-09-02
Features
40 features
What the disease is reported to present with, and how often among people who have it — never how often a feature means the disease. HPO, annotations 2026-09-02.
- Babinski signHPOHP:0003487
- 5 of 5 reported patients
- Very frequent (80% to 99% of cases)
- Cerebellar atrophyHPOHP:0001272
- 2 of 2 reported patients
- Frequent (30% to 79% of cases)
- Cerebral atrophyHPOHP:0002059
- 2 of 2 reported patients
- Frequent (30% to 79% of cases)
- DementiaHPOHP:0000726
- 5 of 5 reported patients
- Occasional (5% to 29% of cases)
- HyperreflexiaHPOHP:0001347
- 5 of 5 reported patients
Genes
1 gene
Germline variants in the gene encoding each protein, as classified by GenCC submitters, each in their own words. Limited, disputed and refuted submissions are listed too.
- GBA2HGNC:18986
- Definitive · G2P · Autosomal recessive · 2025
- Strong · Labcorp Genetics (formerly Invitae) · Autosomal recessive · 2021
- Strong · PanelApp Australia · Autosomal recessive · 2025
- Supportive · Orphanet · Autosomal recessive · 2021
Where it sits
Other names
5 names
Resolves to: hereditary spastic paraplegia 46
- Also called
- autosomal recessive complex spastic paraplegia caused by mutation in GBA2autosomal recessive spastic paraplegia type 46GBA2 autosomal recessive complex spastic paraplegiahereditary spastic paraplegia type 46SPG46