ORPHA:641353
Infantile neurodegeneration-progressive spasticity-intellectual disability-white matter lesions syndrome
Also known as: HPDL-related Leigh-like encephalopathy · HPDL-related infantile neurodegeneration-progressive spasticity-intellectual disability-white matter lesions syndrome
Publications
18
34.8th percentile
Trials
0
Interventional, condition-specific
Researchers
182
Distinct authors in sample
Gene link
GAD1, HPDL
Strong
Readiness
2/6
Stages with a signal
Clinical definition (Orphanet)
A rare genetic neurological syndrome of variable severity characterized by spasticity affecting predominantly the lower limbs. Most patients manifest global , moderate to severe and white matter abnormalities in infancy complicated by variable features including , episodic respiratory failure, joint contractures and ocular problems. Some patients have normal early development until later childhood followed by regression in motor, cognitive and language skills over time. Some patients manifest only spastic paraplegia.
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:0033613
- MeSH:C567853
- OMIM:603513
- OMIM:619026
- UMLS:C5436628
Additional Mondo synonyms (4)
NEDSWMA · cerebral palsy, spastic quadriplegic, 1 · cerebral palsy, spastic quadriplegic, type 1 · infantile neurodegeneration-progressive spasticity-intellectual disability-white matter lesions syndrome
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
Strong — GAD1, HPDL
- LiteraturePresent
18 matched papers (17 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 (GAD1, HPDL).
GenCC classification: Strong.
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?
18
18 papers have ever been indexed 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.
18 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).
17 in the last 10 years · high confidence · 34.8th percentile (publications denominator)
Phrase hits: 18 · MeSH hits: 1
Who's working on it?
182
Distinct author names in 18 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.
- 01Alecu JE2 papers · 2025
Department of Neurology, F.M. Kirby Neurobiology Center, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Papers in Europe PMC - 02Baggiani M2 papers · 2026
Neurobiology and Molecular Medicine Units, , via dei Giacinti 2, Calambrone , ,
Papers in Europe PMC - 03Cappello V2 papers · 2026
Electron Crystallography, Center for Material Interfaces, , Viale Rinaldo Piaggio 34 , , ,
Papers in Europe PMC - 04Damiani D2 papers · 2026
Neurobiology and Molecular Medicine Units, , via dei Giacinti 2, Calambrone , ,
Papers in Europe PMC - 05
- 06Ebrahimi-Fakhari D2 papers · 2025
Department of Neurology, F.M. Kirby Neurobiology Center, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Papers in Europe PMC - 07Galatolo D2 papers · 2026
Neurobiology and Molecular Medicine Units, , via dei Giacinti 2, Calambrone , ,
Papers in Europe PMC - 08Giacich M2 papers · 2026
Neurobiology and Molecular Medicine Units, , via dei Giacinti 2, Calambrone , ,
Papers in Europe PMC - 09Mero S2 papers · 2026
Neurobiology and Molecular Medicine Units, , via dei Giacinti 2, Calambrone , ,
Papers in Europe PMC - 10Naef V2 papers · 2026
Neurobiology and Molecular Medicine Units, , via dei Giacinti 2, Calambrone , ,
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. 2 observational studies did — shown below because natural-history and cohort work can be an important step toward a trial.
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.
Observational and natural-history studies
2 observational studies match this condition. These do not test a treatment and are not counted in the interventional-trial headline, but they are genuine research: natural-history work often defines the endpoints needed for a future rare-disease trial, and families may be able to enroll.
Recruiting or not-yet-recruiting
- NCT05848271·RECRUITING·Natural History Study of Patients with HPDL Mutations
Conditions: Mitochondrial Encephalomyopathies · Hereditary Spastic Paraplegia · Spastic Paraplegia · White Matter Disease·Matched via recall expansion
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.
"Infantile neurodegeneration-progressive spasticity-intellectual disability-white matter lesions syndrome" OR "HPDL-related Leigh-like encephalopathy" OR "HPDL-related infantile neurodegeneration-progressive spasticity-intellectual disability-white matter lesions syndrome" OR "NEDSWMA" OR "cerebral palsy, spastic quadriplegic, 1" OR "cerebral palsy, spastic quadriplegic, type 1"
MeSH descriptor terms unioned into the query: Cerebral Palsy, Spastic Quadriplegic, 1
ClinicalTrials.gov query (quoted phrases + MeSH via query.cond, plus recall-expansion terms when used):
"Infantile neurodegeneration-progressive spasticity-intellectual disability-white matter lesions syndrome" OR "HPDL-related Leigh-like encephalopathy" OR "HPDL-related infantile neurodegeneration-progressive spasticity-intellectual disability-white matter lesions syndrome" OR "NEDSWMA" OR "cerebral palsy, spastic quadriplegic, 1" OR "cerebral palsy, spastic quadriplegic, type 1" OR "GAD1" OR "HPDL"
Recall-expansion terms: GAD1, HPDL
Study-type breakdown: 0 interventional · 2 observational · 0 expanded access. Only interventional studies enter the trial headline.
Query health: ok — strategies attempted: phrase, mesh, recall-expansion; with hits: phrase, mesh, recall-expansion
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 2026-07-27T19:33:38.644Z