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ORPHA:254875

TK2-related mitochondrial DNA maintenance defect, myopathic form

medium confidenceDisorder

Also known as: TK2 deficiency · Thymidine kinase 2 deficiency · TK2d

Query health: suspect — Only one of 2 strategies returned hits (phrase).

Publications

231

65.6th percentile

Trials

4

Interventional, condition-specific

Researchers

1,119

Distinct authors in sample

Gene link

TK2

Definitive

Readiness

5/6

Stages with a signal

Clinical definition (Orphanet)

A rare DNA depletion syndrome characterized by muscle weakness, and , generalized due to depletion of mtDNA in skeletal muscles. Clinical progression ranges from rapid and early fatal course due to respiratory failure, to slowly over the course of childhood or even early adulthood.

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 (2)

mitochondrial DNA depletion syndrome type 2 · mtDNA depletion syndrome, myopathic form

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.

  1. Gene identifiedPresent

    Definitive — TK2

  2. LiteraturePresent

    231 matched papers (173 in last 10 years) Source

  3. Phenotype characterisedPresent

    65 HPO annotations (e.g. Seizure; Hypotonia; Generalized hypotonia) Source

  4. Animal modelPresent

    2 genotype models (Mus musculus) Source

  5. Orphan designationNot found

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

  6. Interventional trialPresent

    4 matched on ClinicalTrials.gov (1 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 (TK2).

GenCC classification: Definitive.

Phenotypes (Monarch / HPO)

65

Associated phenotypes · MONDO:0012301

  • Seizure
  • Hypotonia
  • Generalized hypotonia
  • Abnormal basal ganglia morphology
  • Decreased activity of mitochondrial complex I

Showing 5 of 65 — open Monarch for the full list.

Animal models (Monarch / Alliance)

2

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)

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

2

Drugs / clinical candidates · MONDO_0012301

CTD chemicals (MyDisease.info)

No CTD chemical associations returned for this Mondo ID.

Literature

Is anyone studying this?

231

231 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=3967) is 59.

231 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).

173 in the last 10 years · medium confidence · 65.6th percentile (publications denominator)

Phrase hits: 204 · MeSH hits: 0

Open Europe PMC search

Who's working on it?

1,119

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
    Hirano M35 papers · 2026

    Department of Neurology, Columbia University Medical Center, New York, New York, USA.

    Papers in Europe PMC
  2. 02
    Domínguez-González C17 papers · 2026

    Neuromuscular Unit, Department of Neurology, Hospital Universitario 12 de Octubre, 28041 Madrid, Spain.

    Papers in Europe PMC
  3. 03
    Karlsson A12 papers · 2023

    Karolinska Institute, SE-171 77 Stockholm, Sweden;

    Papers in Europe PMC
  4. 04
    Garone C10 papers · 2026

    Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, 40138 Bologna, Italy; UOC Neuropsichiatria dell'età Pediatrica, IRCCS Istituto delle Scienze Neurologiche di Bologna, 40138 Bologna, Italy. Electronic address: caterina.garone@unibo.it.

    Papers in Europe PMC
  5. 05
    Martí R10 papers · 2026

    Laboratory of Mitochondrial Disorders, Institut de Recerca Hospital Universitari Vall d'Hebron, 08035 Barcelona, Spain.

    Papers in Europe PMC
  6. 06
    Nascimento A10 papers · 2026

    Center for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Madrid, Spain.

    Papers in Europe PMC
  7. 07
    Zhou X9 papers · 2023

    Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institute, Karolinska University Hospital, Stockholm 141 86, Sweden.

    Papers in Europe PMC
  8. 08
    Paradas C8 papers · 2026

    Neuromuscular Disorders Unit, Neurology Department, Hospital Universitario Virgen del Rocío, Sevilla, Spain.

    Papers in Europe PMC
  9. 09
    Scaglia F8 papers · 2026

    Department of Molecular and Human Genetics, Baylor College of Medicine and Texas Children's Hospital, Houston, Texas, USA.

    Papers in Europe PMC
  10. 10
    Vilà MR7 papers · 2011

    Department of Neurology, Columbia University College of Physicians & Surgeons. New York, NY, USA.

    Papers in Europe PMC

Clinical research

Is a treatment being tested?

4

interventional trials for this specific condition

4 interventional trials matched this specific condition name; 1 currently recruiting in our sample.

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

4 interventional trials — more than 77.2% of diseases in the trials denominator have none at all (5501 of 7126; this disease is at the 88.1th percentile).

medium confidence · 88.1th percentile (trials denominator)

Recruiting interventional trials

From the matched ClinicalTrials.gov set

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

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.

Open the complete matched search on ClinicalTrials.gov

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 2 · after dedupe 2 · already on CT.gov 0 · kept 0 · parent 0 · uncertain 2 · 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).

Uncertain / not reviewed (2)

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 TK2-related mitochondrial DNA maintenance defect, myopathic form — 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.

("TK2-related mitochondrial DNA maintenance defect, myopathic form" OR "TK2 deficiency" OR "Thymidine kinase 2 deficiency" OR "mitochondrial DNA depletion syndrome type 2" OR "mtDNA depletion syndrome, myopathic form") OR (MESH:"Mitochondrial DNA Depletion Syndrome, Myopathic Form") OR ("TK2 syndrome" OR "TK2-related")

Run this search on Europe PMC

MeSH descriptor terms unioned into the query: Mitochondrial DNA Depletion Syndrome, Myopathic Form

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

"TK2-related mitochondrial DNA maintenance defect, myopathic form" OR "TK2 deficiency" OR "Thymidine kinase 2 deficiency" OR "mitochondrial DNA depletion syndrome type 2" OR "mtDNA depletion syndrome, myopathic form" OR "Mitochondrial DNA Depletion Syndrome, Myopathic Form"

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: 4 interventional · 1 observational · 0 expanded access. Only interventional studies enter the trial headline.

Query health: suspect — strategies attempted: phrase, mesh; with hits: phrase

Run this search on ClinicalTrials.gov

Synonyms dropped by stoplist: TK2d

Confidence reasoning

  • Preferred label is multi-word and distinctive
  • 1 synonym(s) dropped by stoplist (may under-count)
  • No label/synonym collisions with other diseases in this corpus

Ingested 2026-07-27T11:07:54.569Z