TK2d is a progressive, genetic, and life‑threatening mitochondrial disease.1

It can develop at any point in life, but early onset is defined as TK2d symptom onset that occurs on or before the age of 12.1

TK2d is the result of nuclear DNA mutation in the TK2 gene.1,2

This genetic mutation causes defects in the mitochondrial matrix enzyme, TK2, which is responsible for phosphorylating deoxythymidine (dT) and deoxycytidine (dC).1‑5

These nucleosides are crucial in the production and maintenance of mitochondrial DNA (mtDNA), and therefore, energy metabolism.1‑5

Without these nucleosides muscle damage occurs.1‑4

Normal vs defective mitochondria with TK2.
Normal vs defective mitochondria with TK2.

DNA=deoxyribonucleic acid; TK2d=thymidine kinase 2 deficiency.

Early-onset TK2d predominantly presents as muscle weakness.1

TK2d may impact the ability to walk, eat, and breathe independently. It is often fatal.1

Earlier onset typically results in more severe symptoms that progress faster and result in early death1,6

Once you identify red-flag symptoms, genetic testing is the fastest and only route to confirm a TK2d diagnosis.2,7

It is possible that a person first experiences symptoms as an infant or child but does not get diagnosed until after age 12 due to diagnostic delays. Because of this, it's possible that even those diagnosed as adults may have early-onset TK2d if their symptoms began on or before 12 years old.3,8

Conduct genetic testing early to help your patients seek the care they need.3,9

The TK2 gene is NOT included in all genetic tests. When you suspect TK2d, order testing inclusive of TK2 to definitively diagnose a patient.6,9

3 COMMON GENETIC TESTS TO DIAGNOSE TK2d:6

Whole-exome sequencing/whole-genome sequencing

PREFERRED METHOD

Multi-gene panels that include TK2

Single-gene testing for TK2

A definitive diagnosis is the first step toward treatment for early-onset TK2d.10

Some patients may need additional genetic testing.6,9

PATIENTS WHO HAVE:2,6,10,11

  • Undergone genetic tests that did not include TK2
  • Received negative or inconclusive results on neuromuscular panels or other genetic tests
  • Received unconfirmed diagnoses of diseases that mimic TK2d (eg, neuromuscular disorders, Pompe disease, muscular dystrophy)
  • Not yet received a diagnosis

Order genetic testing inclusive of the TK2 gene.

LET'S CONNECT.

Get more information about early-onset TK2d.

Contact a UCB representative 

References

  1. Garone C, Taylor RW, Nascimento A, et al. Retrospective natural history of thymidine kinase 2 deficiency. J Med Genet. 2018;55(8):515-521. doi:10.1136/jmedgenet-2017-105012
  2. Thymidine kinase 2 deficiency. National Organization for Rare Disorders. Updated March 1, 2026. Accessed March 1, 2026. https://rarediseases.org/rare-diseases/thymidine-kinase-2-deficiency/
  3. Berardo A, Domínguez-González C, Engelstad K, Hirano M. Advances in thymidine kinase 2 deficiency: clinical aspects, translational progress, and emerging therapies. J Neuromuscul Dis. 2022;9(2):225-235. doi:10.3233/JND-210786
  4. Lopez-Gomez C, Levy RJ, Sanchez-Quintero MJ, et al. Deoxycytidine and deoxythymidine treatment for thymidine kinase 2 deficiency. Ann Neurol. 2017;81(5):641-652. doi:10.1002/ana.24922
  5. Lopez-Gomez C, Hewan H, Sierra C, et al. Bioavailability and cytosolic kinases modulate response to deoxynucleoside therapy in TK2 deficiency. EBioMedicine. 2019;46:356-367. doi:10.1016/j. ebiom.2019.07.037
  6. Wang J, El-Hattab AW, Wong LJC. TK2-related mitochondrial DNA maintenance defect, myopathic form. In: Adam MP, Feldman J, Mirzaa GM, et al, eds. GeneReviews®. [Internet]. Seattle (WA): University of Washington, Seattle; December 6, 2012.
  7. Ng KWP, Chin HL, Chin AXY, Goh DLM. Using gene panels in the diagnosis of neuromuscular disorders: a mini-review. Front Neurol. 2022;13:997551. doi:10.3389/fneur.2022.997551
  8. Manini A, Meneri M, Rodolico C, et al. Case report: thymidine kinase 2 (TK2) deficiency: a novel mutation associated with childhood-onset mitochondrial myopathy and atypical progression. Front Neurol. 2022;13:857279. doi:10.3389/fneur.2022.857279
  9. Domínguez-González C, Madruga-Garrido M, Hirano M, et al. Collaborative model for diagnosis and treatment of very rare diseases: experience in Spain with thymidine kinase 2 deficiency. Orphanet J Rare Dis. 2021;16(1):407. doi:10.1186/s13023-021-02030-w
  10. Nicolau S, Milone M, Liewluck T. Guidelines for genetic testing of muscle and neuromuscular junction disorders. Muscle Nerve. 2021;64(3):255-269. doi:10.1002/mus.27337
  11. Grier J, Hirano M, Karaa A, Shepard E, Thompson JLP. Diagnostic odyssey of patients with mitochondrial disease: results of a survey. Neurol Genet. 2018;4(2):e230. doi:10.1212/NXG.0000000000000230

INDICATION

KYGEVVI is indicated for the treatment of thymidine kinase 2 deficiency (TK2d) in adults and pediatric patients with an age of symptom onset on or before 12 years.

IMPORTANT SAFETY INFORMATION

Increase in Liver Transaminases

Elevated liver transaminase [alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST)] levels were reported in patients treated with KYGEVVI. Obtain baseline liver transaminase (ALT, AST) and total bilirubin levels in patients prior to treatment initiation with KYGEVVI.

INDICATION

KYGEVVI is indicated for the treatment of thymidine kinase 2 deficiency (TK2d) in adults and pediatric patients with an age of symptom onset on or before 12 years.

IMPORTANT SAFETY INFORMATION

Increase in Liver Transaminases

Elevated liver transaminase [alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST)] levels were reported in patients treated with KYGEVVI. Obtain baseline liver transaminase (ALT, AST) and total bilirubin levels in patients prior to treatment initiation with KYGEVVI. If signs or symptoms consistent with liver injury are observed, interrupt treatment with KYGEVVI until liver transaminase (ALT, AST) and total bilirubin levels have either returned to baseline or stabilized at a new baseline value. Consider permanently discontinuing KYGEVVI if signs or symptoms consistent with liver injury persist or worsen. Monitor liver transaminases and total bilirubin levels yearly and as clinically indicated.

Gastrointestinal Adverse Reactions 

Diarrhea and vomiting leading to hospitalization, dose reduction, and permanent discontinuation were reported in patients treated with KYGEVVI. Based on the severity of the diarrhea and/or vomiting, reduce the dosage of KYGEVVI or interrupt treatment until diarrhea and/or vomiting improves or returns to baseline. Consider restarting KYGEVVI at the last tolerated dose, and increase the dose as tolerated. For persistent or recurring diarrhea and/or vomiting, consider discontinuing KYGEVVI permanently and provide supportive care with electrolyte repletion as clinically indicated.

Adverse Reactions

The most common adverse reactions (incidence ≥5%) are diarrhea, abdominal pain (including abdominal pain upper), vomiting, alanine aminotransferase increased (ALT), and aspartate aminotransferase increased (AST).

Please see the full Prescribing Information.