RARE DISEASERESEARCH ATLAS
Open navigation menu

ORPHA:320391

Autosomal recessive spastic paraplegia type 46

low confidenceDisorder

Also known as: SPG46

Publications

16,851

Trials

0

Interventional, condition-specific

Researchers

832

Distinct authors in sample

Gene link

GBA2

Definitive

Readiness

3/6

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.

Orphanet entry

Cross-references

Joined from Mondo / Orphanet. MeSH labels may enter searches; UMLS / OMIM / NCIT are stored for reference.

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.”

3/6 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.

  1. Gene identifiedPresent

    Definitive — GBA2

  2. LiteraturePresent

    16,851 matched papers (9,910 in last 10 years) Source

  3. Phenotype characterisedPresent

    66 HPO annotations (e.g. Cataract; Cerebellar atrophy; Abnormal cerebral white matter morphology) Source

  4. Animal modelNot found

    No Alliance genotype “model of” associations via Monarch for these Mondo IDs

  5. Orphan designationNot found

    No FDA or EMA orphan-drug designation matched this disease via UMLS or preferred name Source

  6. 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)

66

Associated phenotypes · MONDO:0013737

  • Cataract
  • Cerebellar atrophy
  • Abnormal cerebral white matter morphology
  • Hearing impairment
  • Infertility

Showing 5 of 66 — open Monarch for the full list.

Animal models (Monarch / Alliance)

None returned for this Mondo ID. Empty here is not proof that no model organism work exists under another name or gene.

Monarch fetch 2026-07-29

Therapies

Designations, candidates, and chemicals

FDA OOPD and EMA orphan designations, Open Targets clinical candidates, and CTD chemical associations via MyDisease.info. These never change the interventional-trial headline.

Orphan designation (FDA · EMA)

No designation matched this disease via UMLS or preferred name on the FDA OOPD mirror or EMA orphan register. Absence here is not proof that none exists under another wording.

Open Targets candidates

No drugs or clinical candidates returned for this Mondo ID on Open Targets.

CTD chemicals (MyDisease.info)

No CTD chemical associations returned for this Mondo ID.

Literature

Is anyone studying this?

16,851

16,851 papers — among the better-studied rare conditions, though still a fraction of common-disease literature (breast cancer: over 700,000). Median papers in the last 10 years for a rare disease in this dataset (publications denominator n=3967) is 59.

16,851 papers since the earliest indexed year in this search — median last-10-year count for a rare disease in this dataset is 59 (publications denominator n=3967).

9,910 in the last 10 years · low confidence

Phrase hits: 111 · MeSH hits: 0

Open Europe PMC search

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.

  1. 01
    Stevanin 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
  2. 02
    Pedroso JL6 papers · 2026

    Ataxia Unit, Department of Neurology, Universidade Federal de São Paulo, São Paulo, SP, Brazil.

    Papers in Europe PMC
  3. 03
    Santorelli FM6 papers · 2026

    Molecular Medicine Unit, IRCCS Fondazione Stella Maris, 56018 Pisa, Italy.

    Papers in Europe PMC
  4. 04
    Schüle 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
  5. 05
    Brice 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
  6. 06
    Durr 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
  7. 07
    Houlden H5 papers · 2026

    Department of Molecular Neuroscience, Institute of Neurology, University College London, London WC1N 3BG, UK.

    Papers in Europe PMC
  8. 08
    Tsuji S5 papers · 2020

    The University of Tokyo, Tokyo, Japan.

    Papers in Europe PMC
  9. 09
    Barsottini OGP4 papers · 2026

    Department of Neurology, Federal University of São Paulo (UNIFESP), São Paulo, Brazil.

    Papers in Europe PMC
  10. 10
    Darios 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 11 September 2026 · last trial check 11 September 2026

No matched interventional trials. This is true for 77.2% of diseases in the trials denominator (5501 of 7126). Here are the researchers publishing on it.

low confidence · 38.6th 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.

Other registries (secondary)

Broader net from EU CTIS, ISRCTN, and ICTRP when available — deduped against ClinicalTrials.gov IDs already counted above. Dual-model LLM relevance gates what we keep. These rows are not added to the interventional headline.

raw 0 · after dedupe 0 · already on CT.gov 0 · kept 0 · parent 0 · uncertain 0 · dropped 0 · fetched 2026-07-30

Source notes: ictrp: Error: ICTRP public search unavailable (WHO portal is SPA-only; SOAP needs partnership). Tried: https://apps.who.int/tri

No secondary-registry studies passed dual-model relevance for this condition name (after dedupe).

Where to find support

Condition-specific patient organisations, when Orphanet lists them, are on the disease’s Orphanet page. We also link umbrella groups that support undiagnosed and ultra-rare families.

Orphanet entry for Autosomal recessive spastic paraplegia type 46 — check Associations / patient organisations on that page.

India — NPRD

Last verified 2026-07-26

This 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") OR ("GBA2" OR "GBA2 syndrome" OR "GBA2-related")

Run this search on Europe PMC

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"

Study-type breakdown: 0 interventional · 0 observational · 0 expanded access. Only interventional studies enter the trial headline.

Query health: ok — strategies attempted: phrase; 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
  • Publication count (16851) is implausibly high for prevalence class "<1 / 1 000 000" — treat as possible over-matching, not a measure of research intensity

Ingested 2026-07-27T13:33:13.444Z