ORPHA:320391
Autosomal recessive spastic paraplegia type 46
Also known as: SPG46
Query health: suspect — Only one of 2 strategies returned hits (phrase).
Publications
111
64.7th percentile
Trials
0
Interventional, condition-specific
Researchers
832
Distinct authors in sample
Gene link
GBA2
Definitive
Readiness
2/6
Stages with a signal
Clinical definition (Orphanet)
spastic paraplegia type 46 (SPG46) is a rare, complex type of 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 , 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.
How rare: <1 / 1 000 000 — fewer than one in a million. In a city the size of Kolkata, that might mean on the order of fifteen people.
Cross-references
Joined from Mondo / Orphanet. MeSH labels may enter searches; UMLS / OMIM / NCIT are stored for reference.
- MONDO:0013737
- OMIM:614409
- UMLS:C2828721
Additional Mondo synonyms (5)
GBA2 autosomal recessive complex spastic paraplegia · autosomal recessive complex spastic paraplegia caused by mutation in GBA2 · autosomal recessive spastic paraplegia type 46 · hereditary spastic paraplegia 46 · hereditary spastic paraplegia type 46
Research stages
Trial readiness signals
Where this condition sits on an open-data research pipeline — not how close a treatment is, and not medical advice. Empty stages often mean “not in these databases under this Mondo ID,” not “impossible.”
2/6 stages with a signal
No matched interventional trial; the gene is known and literature exists — preclinical or natural-history work may still be the practical next step.
- Gene identifiedPresent
Definitive — GBA2
- LiteraturePresent
111 matched papers (90 in last 10 years) Source
- Phenotype characterisedNot checked
Not yet enriched from Monarch / HPO
- Animal modelNot checked
Not yet enriched from Monarch / Alliance
- Orphan designationNot checked
FDA/EMA orphan-drug designation not enriched yet
- Interventional trialNot found
No matched interventional trial under our ClinicalTrials.gov rules
Biology
Genes and phenotypes
Gene–disease validity from GenCC, plus phenotypes and animal models joined from Monarch Initiative via Mondo ID — not a clinical diagnosis aid.
Do we know what causes it?
Yes — we know a specific gene responsible (GBA2).
GenCC classification: Definitive.
Phenotypes (Monarch / HPO)
Not enriched in this build — Monarch phenotype joins were not run for this record.
Animal models (Monarch / Alliance)
Not enriched in this build.
Literature
Is anyone studying this?
111
111 papers have ever been published on this condition (under this name). For scale, breast cancer has over 700,000. Median papers in the last 10 years for a rare disease in this dataset (publications denominator n=5449) is 41.
111 papers since the earliest indexed year in this search — median last-10-year count for a rare disease in this dataset is 41 (publications denominator n=5449).
90 in the last 10 years · high confidence · 64.7th percentile (publications denominator)
Phrase hits: 111 · MeSH hits: 0
Who's working on it?
832
Distinct author names in 111 sampled papers — named people below.
Who's working on it?
No interventional trial matched this name; these authors publish on it in the sampled literature — a practical starting point for contact.
- 01Stevanin G9 papers · 2025
Institut National de la Santé et de la Recherche Médicale U1127, 75013 Paris, France; Centre National de la Recherche Scientifique UMR 7225, 75013 Paris, France; Sorbonne Universités, Université Pierre et Marie Curie (Paris 6) UMR_S 1127, Institut du Cerveau et de la Moelle Épinière, 75013 Paris, France; Neurogenetics team, École Pratique des Hautes Études, HéSam Université, 75013 Paris, France; Fédération de Génétique, Pitié-Salpêtrière Hospital, Assistance Publique - Hôpitaux de Paris, 75013 Paris, France.
Papers in Europe PMC - 02Pedroso JL6 papers · 2026
Ataxia Unit, Department of Neurology, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
Papers in Europe PMC - 03Santorelli FM6 papers · 2026
Molecular Medicine Unit, IRCCS Fondazione Stella Maris, 56018 Pisa, Italy.
Papers in Europe PMC - 04Schüle R6 papers · 2021
Department for Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research, Hoppe-Seyler-Strasse 3, University of Tubingen, 72077, Tubingen, Germany; German Research Center for Neurodegenerative Diseases (DZNE), University of Tubingen, 72076, Tuebingen, Germany; Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL, 33136, USA.
Papers in Europe PMC - 05Brice A5 papers · 2016
Institut National de la Santé et de la Recherche Médicale U1127, 75013 Paris, France; Centre National de la Recherche Scientifique UMR 7225, 75013 Paris, France; Sorbonne Universités, Université Pierre et Marie Curie (Paris 6) UMR_S 1127, Institut du Cerveau et de la Moelle Épinière, 75013 Paris, France; Fédération de Génétique, Pitié-Salpêtrière Hospital, Assistance Publique - Hôpitaux de Paris, 75013 Paris, France.
Papers in Europe PMC - 06Durr A5 papers · 2021
Institut National de la Santé et de la Recherche Médicale U1127, 75013 Paris, France; Centre National de la Recherche Scientifique UMR 7225, 75013 Paris, France; Sorbonne Universités, Université Pierre et Marie Curie (Paris 6) UMR_S 1127, Institut du Cerveau et de la Moelle Épinière, 75013 Paris, France; Fédération de Génétique, Pitié-Salpêtrière Hospital, Assistance Publique - Hôpitaux de Paris, 75013 Paris, France.
Papers in Europe PMC - 07Houlden H5 papers · 2026
Department of Molecular Neuroscience, Institute of Neurology, University College London, London WC1N 3BG, UK.
Papers in Europe PMC - 08
- 09Barsottini OGP4 papers · 2026
Department of Neurology, Federal University of São Paulo (UNIFESP), São Paulo, Brazil.
Papers in Europe PMC - 10Darios F4 papers · 2021
Institut du Cerveau et de la Moelle épinière, INSERM U1127, CNRS UMR7225, Sorbonne Universités, UPMC Université Paris VI UMR_S1127, Paris, France.
Papers in Europe PMC
Clinical research
Is a treatment being tested?
0
interventional trials for this specific condition
No interventional trial testing a treatment matched this specific condition name on ClinicalTrials.gov (observational studies and pan-disease registries are listed separately when present).
Data as of 27 July 2026
No matched interventional trials. This is true for 73% of diseases in the trials denominator (5114 of 7003). Here are the researchers publishing on it.
high confidence · 36.5th percentile (trials denominator)
Recruiting interventional trials
From the matched ClinicalTrials.gov set
No interventional trial testing a treatment was found for this specific condition name on ClinicalTrials.gov.
See who's working on it — people publishing on this disease are often the practical next contact when no trial is listed.
Where to find support
We do not yet link condition-specific patient organisations. These umbrella groups support undiagnosed and ultra-rare families:
India — NPRD
Last verified 2026-07-26This ORPHAcode is not on our curated NPRD list (direct or Mondo-parent match). That does not decide clinical eligibility; families in India should ask a notified Centre of Excellence about current coverage.
Hand-curated for this project. ORPHAcode mappings are best-effort and may be incomplete or imprecise for umbrella categories. Parent (Mondo) matches mean the policy lists a broader category — confirm eligibility with a Centre of Excellence. Financial entitlements summarised from public policy statements and may change. This is not official government guidance.
How we counted this
Europe PMC query (preferred label + any corrected label + Orphanet and Mondo exact synonyms, stoplisted; unioned with resolved MeSH labels when available). UMLS / OMIM / NCIT cross-references are stored on the overview but are not added to the query string.
"Autosomal recessive spastic paraplegia type 46" OR "SPG46" OR "GBA2 autosomal recessive complex spastic paraplegia" OR "autosomal recessive complex spastic paraplegia caused by mutation in GBA2" OR "hereditary spastic paraplegia 46" OR "hereditary spastic paraplegia type 46"
ClinicalTrials.gov query (quoted phrases + MeSH via query.cond, plus recall-expansion terms when used):
"Autosomal recessive spastic paraplegia type 46" OR "SPG46" OR "GBA2 autosomal recessive complex spastic paraplegia" OR "autosomal recessive complex spastic paraplegia caused by mutation in GBA2" OR "hereditary spastic paraplegia 46" OR "hereditary spastic paraplegia type 46" OR "GBA2"
Recall-expansion terms: GBA2
Study-type breakdown: 0 interventional · 0 observational · 0 expanded access. Only interventional studies enter the trial headline.
Query health: suspect — strategies attempted: phrase, recall-expansion; with hits: phrase
Run this search on ClinicalTrials.gov
Confidence reasoning
- Preferred label is multi-word and distinctive
- No synonyms dropped by stoplist
- No label/synonym collisions with other diseases in this corpus
Ingested 2026-07-27T13:33:13.444Z