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ORPHA:506

Leigh syndrome

low confidenceDisorder

Also known as: Infantile subacute necrotizing encephalopathy · Leigh disease

Publications

18,259

Trials

8

Interventional, condition-specific

Researchers

1,501

Distinct authors in sample

Gene link

ADAR, AIFM1, ATP5MK

Definitive

Readiness

6/6

Stages with a signal

Clinical definition (Orphanet)

A neurological disease defined by specific neuropathological features associating brainstem and basal ganglia lesions.

How rare: How common this is has not been clearly measured.

Orphanet entry

Cross-references

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

Additional Mondo synonyms (5)

LS · LSS · Leigh syndrome spectrum · Leigh's disease · infantile subacute necrotizing encephalopathy

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.”

6/6 stages with a signal

An interventional trial matched this condition name on ClinicalTrials.gov — see trials below.

  1. Gene identifiedPresent

    Definitive — ADAR, AIFM1, ATP5MK, BCS1L, BTD…

  2. LiteraturePresent

    18,259 matched papers (11,904 in last 10 years) Source

  3. Phenotype characterisedPresent

    315 HPO annotations (e.g. Spasticity; Poor speech; Dysphagia) Source

  4. Animal modelPresent

    9 genotype models (Mus musculus, Danio rerio) Source

  5. Orphan designationPresent

    1 FDA · 6 EMA designations (1 FDA orphan-indication approval) — e.g. vatiquinone Source

  6. Interventional trialPresent

    8 matched on ClinicalTrials.gov (2 recruiting in sample)

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 (ADAR, AIFM1, ATP5MK…).

GenCC classification: Definitive.

Phenotypes (Monarch / HPO)

315

Associated phenotypes · MONDO:0009723

  • Spasticity
  • Poor speech
  • Dysphagia
  • Dyskinesia
  • Inability to walk

Showing 5 of 315 — open Monarch for the full list.

Animal models (Monarch / Alliance)

9

Model associations linked to this Mondo ID

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)

7

Designations · 1 with FDA orphan-indication approval

  • FDA vatiquinoneLeigh Syndrome · 2014-06-04 · Not FDA Approved for Orphan Indication
  • EMA cannabidiolTreatment of Leigh syndrome · 25/07/2023 · PositiveEMA designation
  • EMA Methyl 4-(2-acetamidoethylsulfanyl)-4-oxobutanoateTreatment of Leigh syndrome · 13/12/2023 · PositiveEMA designation
  • EMA sildenafil citrateTreatment of Leigh syndrome · 13/10/2023 · PositiveEMA designation
  • EMA (S)-6-hydroxy-2,5,7,8-tetramethyl-N-((R)-piperidin-3-yl)chroman-2-carboxamide hydrochlorideTreatment of Leigh syndrome · 15/10/2014 · WithdrawnEMA designation
  • EMA adeno-associated viral vector serotype 9 containing the human SURF1 geneTreatment of Leigh syndrome · 12/11/2021 · WithdrawnEMA designation
  • EMA alpha-tocotrienol quinoneTreatment of Leigh syndrome · 09/12/2011 · WithdrawnEMA designation

Sources: FDA OOPD · EMA orphan designations

Open Targets candidates

7

Drugs / clinical candidates · MONDO_0009723

CTD chemicals (MyDisease.info)

3 associated chemicals · 39 pathways. Therapeutic evidence is listed first when present — not a treatment recommendation.

  • acryloyl-coenzyme A · marker/mechanism
  • methacrylyl-coenzyme A · marker/mechanism
  • S-(2-carboxypropyl)cysteine · marker/mechanism

Pathways: Fatty acid elongation; Fatty acid degradation; Oxidative phosphorylation; Valine, leucine and isoleucine degradation; Lysine degradation; Tryptophan metabolism; beta-Alanine metabolism; Propanoate metabolism

MyDisease.info · MONDO:0009723

Literature

Is anyone studying this?

18,259

18,259 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.

18,259 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).

11,904 in the last 10 years · low confidence

Phrase hits: 6,446 · MeSH hits: 0

Open Europe PMC search

Who's working on it?

1,501

Distinct author names in 200 sampled papers — named people below.

Who's working on it?

People publishing on this condition (sampled Europe PMC records). Affiliation is the most recent found in that sample.

  1. 01
    Murayama K10 papers · 2026

    Department of Metabolism, Chiba Children's Hospital, Japan.

    Papers in Europe PMC
  2. 02
    Rahman S10 papers · 2025

    Genetics and Genomic Medicine Department, UCL Great Ormond Street Institute of Child Health, London, United Kingdom; Metabolic Medicine Department, Great Ormond Street Hospital for Children, London, United Kingdom. Electronic address: shamima.rahman@ucl.ac.uk.

    Papers in Europe PMC
  3. 03
    Fang F8 papers · 2026

    Department of Neurology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.

    Papers in Europe PMC
  4. 04
    Finsterer J8 papers · 2026

    Neurology & Neurophysiology Center, Austria.

    Papers in Europe PMC
  5. 05
    Falk MJ7 papers · 2025

    Mitochondrial Medicine Frontier Program, Division of Human Genetics, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, USA; Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

    Papers in Europe PMC
  6. 06
    Johnson SC7 papers · 2026

    Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, Washington, USA.

    Papers in Europe PMC
  7. 07
    Chen Y6 papers · 2026

    Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, Washington, USA.

    Papers in Europe PMC
  8. 08
    Ohtake A6 papers · 2026

    Department of Clinical Genomics, Faculty of Medicine, Saitama Medical University, Moroyama 350-0495, Japan.

    Papers in Europe PMC
  9. 09
    James K5 papers · 2026

    Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, Washington, USA.

    Papers in Europe PMC
  10. 10
    Klopstock T5 papers · 2026

    Department of Neurology, Friedrich-Baur-Institute, University Hospital, Ludwig-Maximilians-Universität (LMU) München, Munich, Germany; German Center for Neurodegenerative Diseases (DZNE), Munich, Germany; Munich Cluster for Systems Neurology (SyNergy), Munich, Germany; German Network for mitochondrial disorders (mitoNET), Munich, Germany.

    Papers in Europe PMC

Clinical research

Is a treatment being tested?

8

interventional trials for this specific condition

8 interventional trials matched this specific condition name; 2 currently recruiting in our sample.

Data as of 11 September 2026 · last trial check 28 July 2026

8 interventional trials — more than 77.2% of diseases in the trials denominator have none at all (5501 of 7126; this disease is at the 91.5th percentile).

low confidence · 91.5th percentile (trials denominator)

Recruiting interventional trials

From the matched ClinicalTrials.gov set

8 interventional trials matched after quoted-phrase search and title/condition post-filter.

Observational and natural-history studies

6 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

Open the complete matched search on ClinicalTrials.gov

General rare disease registries you may be eligible for

These studies enroll across many rare conditions. They are not counted as evidence that anyone is studying this specific disease.

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 28 · after dedupe 28 · already on CT.gov 0 · kept 0 · parent 0 · uncertain 28 · dropped 0 · fetched 2026-07-29

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).

Uncertain / not reviewed (28)

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 Leigh syndrome — 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.

("Leigh syndrome" OR "Infantile subacute necrotizing encephalopathy" OR "Leigh disease" OR "Leigh syndrome spectrum" OR "Leigh's disease") OR ("ADAR" OR "ADAR syndrome" OR "ADAR-related" OR "AIFM1" OR "AIFM1 syndrome" OR "AIFM1-related" OR "ATP5MK" OR "ATP5MK syndrome" OR "ATP5MK-related")

Run this search on Europe PMC

ClinicalTrials.gov query (quoted phrases + MeSH via query.cond, plus recall-expansion terms when used):

"Leigh syndrome" OR "Infantile subacute necrotizing encephalopathy" OR "Leigh disease" OR "Leigh syndrome spectrum" OR "Leigh's disease"

Interventional trials matched via: phrase (mesh = registered under a MeSH descriptor no name phrase would catch; recall-expansion = gene / selected parent terms used only for trials).

Study-type breakdown: 8 interventional · 6 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

Synonyms dropped by stoplist: LS; LSS

Confidence reasoning

  • Preferred label is short or not clearly distinctive
  • 2 synonym(s) dropped by stoplist (may under-count)
  • No label/synonym collisions with other diseases in this corpus

Ingested 2026-07-26T14:05:15.981Z