ORPHA:726
Alpers-Huttenlocher syndrome
Also known as: Alpers progressive sclerosing poliodystrophy · Alpers syndrome · Progressive neuronal degeneration of childhood with liver disease
Publications
5,792
93.5th percentile
Trials
1
Interventional, condition-specific
Researchers
1,248
Distinct authors in sample
Gene link
POLG
Definitive
Readiness
5/6
Stages with a signal
Clinical definition (Orphanet)
A cerebrohepatopathy and a rare and severe form of DNA (mtDNA) depletion syndrome characterized by the triad of developmental regression, intractable , and hepatic failure.
How rare: 1-9 / 1 000 000 — roughly one to nine people per million. In a city the size of Kolkata, perhaps a few dozen.
Cross-references
Joined from Mondo / Orphanet. MeSH labels may enter searches; UMLS / OMIM / NCIT are stored for reference.
- MONDO:0008758
- OMIM:203700
- UMLS:C0205710
- NCIT:C35257
Additional Mondo synonyms (14)
AHD · AHS · Alper syndrome · Alper's disease · Alper's syndrome · Alpers Disease · Alpers Huttenlocher disease · Alpers Huttenlocher syndrome · Alpers disease · Alpers progressive infantile poliodystrophy · Alpers-Huttenlocher · mitochondrial DNA depletion syndrome 4A · mitochondrial DNA depletion syndrome type 4a · progressive neuronal degeneration of childhood with liver disease
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.”
5/6 stages with a signal
An interventional trial matched this condition name on ClinicalTrials.gov — see trials below.
- Gene identifiedPresent
Definitive — POLG
- LiteraturePresent
5,792 matched papers (3,838 in last 10 years) Source
- Phenotype characterisedPresent
66 HPO annotations (e.g. Ataxia; Hypotonia; Spasticity) Source
- Animal modelNot found
No Alliance genotype “model of” associations via Monarch for these Mondo IDs
- Orphan designationPartial
1 EMA designation (none yet with FDA orphan-indication approval) — e.g. vatiquinone Source
- Interventional trialPresent
1 matched on ClinicalTrials.gov
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 (POLG).
GenCC classification: Definitive.
Phenotypes (Monarch / HPO)
66
Associated phenotypes · MONDO:0008758
- Ataxia
- Hypotonia
- Spasticity
- Progressive spasticity
- Coma
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)
1
Designation · no FDA orphan-indication approval yet
- EMA vatiquinoneTreatment of Alpers-Huttenlocher syndrome · 10/12/2021 · WithdrawnEMA designation
Sources: FDA OOPD · EMA orphan designations
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?
5,792
5,792 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.
5,792 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).
3,838 in the last 10 years · medium confidence · 93.5th percentile (publications denominator)
Phrase hits: 1,278 · MeSH hits: 0
Who's working on it?
1,248
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.
- 01Finsterer J9 papers · 2025
Danube University Krems, Krems, Austria. fifigs1@yahoo.de
Papers in Europe PMC - 02Copeland WC6 papers · 2025
Mitochondrial DNA Replication Group, Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences (NIEHS), NIH, Research Triangle Park, NC 27709, USA.
Papers in Europe PMC - 03Saneto RP6 papers · 2025
Center for Integrative Brain Research, Neuroscience Institute, Seattle, WA 98101, USA.
Papers in Europe PMC - 04
- 05Cohen BH4 papers · 2025
Department of Pediatrics, Children's Hospital Medical Center of Akron and Northeast Ohio Medical University, Akron, OH, USA.
Papers in Europe PMC - 06Gorman GS4 papers · 2025
Wellcome Centre for Mitochondrial Research Institute of Neuroscience Newcastle University Newcastle United Kingdom.
Papers in Europe PMC - 07McFarland R4 papers · 2025
Wellcome Centre for Mitochondrial Research Institute of Neuroscience Newcastle University Newcastle United Kingdom.
Papers in Europe PMC - 08Rahman S4 papers · 2021
Mitochondrial Research Group, Genetics and Genomic Medicine, UCL Institute of Child Health, London WC1N 1EH, United Kingdom.
Papers in Europe PMC - 09Chen A3 papers · 2026
Department of Neurosurgery, Xinhua Hospital Affiliated with Shanghai Jiaotong University School of Medicine, Shanghai, China.
Papers in Europe PMC - 10Chen S3 papers · 2025
Department of Pediatric Cardiology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Papers in Europe PMC
Clinical research
Is a treatment being tested?
1
interventional trials for this specific condition
1 interventional trial matched this specific condition name; none in our sample are currently recruiting.
Data as of 11 September 2026 · last trial check 28 July 2026
1 interventional trial — more than 77.2% of diseases in the trials denominator have none at all (5501 of 7126; this disease is at the 80.1th percentile).
medium confidence · 80.1th percentile (trials denominator)
Recruiting interventional trials
From the matched ClinicalTrials.gov set
1 interventional trials matched after quoted-phrase search and title/condition post-filter.
No currently recruiting studies in the matched set. Open the same search on ClinicalTrials.gov.
Observational and natural-history studies
1 observational study matches 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.
None of the matched observational studies is currently listed as recruiting.
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 2026-07-29
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).
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 Alpers-Huttenlocher syndrome — check Associations / patient organisations on that page.
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.
("Alpers-Huttenlocher syndrome" OR "Alpers progressive sclerosing poliodystrophy" OR "Alpers syndrome" OR "Progressive neuronal degeneration of childhood with liver disease" OR "Progressive neuronal degeneration of the childhood with liver disease" OR "Alper syndrome" OR "Alper's disease" OR "Alper's syndrome" OR "Alpers Disease" OR "Alpers Huttenlocher disease" OR "Alpers Huttenlocher syndrome" OR "Alpers progressive infantile poliodystrophy" OR "Alpers-Huttenlocher" OR "mitochondrial DNA depletion syndrome 4A" OR "mitochondrial DNA depletion syndrome type 4a") OR ("POLG" OR "POLG syndrome" OR "POLG-related")ClinicalTrials.gov query (quoted phrases + MeSH via query.cond, plus recall-expansion terms when used):
"Alpers-Huttenlocher syndrome" OR "Alpers progressive sclerosing poliodystrophy" OR "Alpers syndrome" OR "Progressive neuronal degeneration of childhood with liver disease" OR "Progressive neuronal degeneration of the childhood with liver disease" OR "Alper syndrome" OR "Alper's disease" OR "Alper's syndrome" OR "Alpers Disease" OR "Alpers Huttenlocher disease" OR "Alpers Huttenlocher syndrome" OR "Alpers progressive infantile poliodystrophy" OR "Alpers-Huttenlocher" OR "mitochondrial DNA depletion syndrome 4A" OR "mitochondrial DNA depletion syndrome type 4a"
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: 1 interventional · 1 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: AHD; AHS
Confidence reasoning
- Preferred label is multi-word and distinctive
- 2 synonym(s) dropped by stoplist (may under-count)
- No label/synonym collisions with other diseases in this corpus
Ingested 2026-07-26T15:03:53.653Z