Thymidine kinase 2 deficiency

By Sudha Thakor

Thymidine kinase 2 deficiency (TK2d) is a rare, autosomal recessive mitochondrial DNA (mtDNA) depletion syndrome with a reported prevalence of 1.64 per million people worldwide.^1,2 It primarily manifests as a progressive mitochondrial myopathy. Pathogenic variants in the TK2 gene impair the mitochondrial nucleotide salvage pathway, leading to reduced mtDNA maintenance and compromised cellular energy production, particularly in skeletal muscle.²

The disease shows marked phenotypic heterogeneity, with onset ranging from infancy to adulthood. Disease severity and rate of progression closely correlate with age at onset, underscoring the importance of early recognition and accurate molecular diagnosis.³ 

Don’t miss: On-demand symposium on advancing TK2d management

Register now to access Medthority’s EBAC-accredited, on-demand symposium: “Advancing TK2d management: From natural history to clinical evidence and real-world opportunities.”

In this symposium – taking place at ICNMD 2026 – Caterina Garone, Yolanda Cámara, and Cristina Domínguez González will explore disease mechanisms in thymidine kinase 2 deficiency (TK2d), emerging clinical evidence, and real-world insights to support efficient diagnosis, patient monitoring, and effective treatment.

If you’re unable to attend ICNMD this year, register below and we’ll let you know as soon as this symposium becomes available to watch on demand.

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Agenda

Meet the experts

Caterina Garone, MD, PhD

Caterina Garone is Associate Professor of Medical Genetics at Alma Mater Studiorum, University of Bologna, Italy, and a pediatric neurologist at UOC Neuropsichiatria dell'Età Pediatrica, S. Orsola Hospital.

Garone specializes in clinical and translational research on metabolic disorders, mitochondrial diseases, neuromuscular diseases, and human genetics, with a particular focus as a neurogeneticist.

Disclosures: Serves on an advisory board of UCB Pharma. Received funding from UCB Pharma for research projects relating to TK2d.

Yolanda Cámara, PhD

Yolanda Cámara is a Principal Investigator at Vall d’Hebron Institute of Research, Barcelona, Spain.

Cámara specializes in neuromuscular and mitochondrial pathology, with her research focused on the molecular mechanisms underlying mitochondrial diseases and disorders of oxidative metabolism, spanning both basic and translational research.

Disclosures: No disclosures reported.

Cristina Domínguez González, MD, PhD

Cristina Domínguez González leads multidisciplinary clinical and research groups at the Hospital 12 de Octubre in Madrid, Spain.

Domínguez González’s area of expertise lies in genetic myopathies, with a particular focus on those originating from metabolic and mitochondrial factors.

Disclosures: Consulting fees from Amicus Therapeutics, Exeltis, Italfarmaco, Modis Therapeutics, Pharmanext, Roche, Sarepta, Sanofi–Genzyme, UCB Pharma, and Zogenix. Research funding from Pretzel Therapeutics and UCB Pharma. Honoraria from Amicus Therapeutics, Roche, Sanofi–Genzyme, and UCB Pharma.

Developed by EPG Health. This content has been developed independently of the sponsor, UCB, which had no editorial input into the content. EPG Health received unrestricted educational funding from the sponsor in order to help provide its healthcare professional members with access to the highest quality medical and scientific information, education, and associated relevant content. This content is intended for healthcare professionals only.

What are the key clinical features of TK2d?

Progressive muscle weakness is the hallmark feature of TK2d across all disease subtypes. Patients may develop:

• Hypotonia
• Loss of motor milestones
• Dysphagia
• Ptosis
• Ophthalmoparesis
• Respiratory muscle weakness, which frequently necessitates ventilatory support

Extramuscular manifestations, such as seizures and hearing loss, occur less commonly.³

How is TK2d diagnosed? 

A diagnosis of TK2d relies on molecular genetic testing to identify biallelic pathogenic variants in TK2. Supportive findings may include:⁴

• Elevated creatine kinase levels
• Myopathic changes observed via electromyography
• Evidence of mtDNA depletion in muscle tissue

What treatment options are available for TK2d?

TK2d management approaches have shifted with the emergence of disease‑modifying therapy. Oral deoxynucleoside therapy can stabilize or improve motor and respiratory function by bypassing the defective TK2 enzyme.¹ Multidisciplinary supportive care remains essential throughout the disease course.⁵

Why is early diagnosis of TK2d important?

Earlier diagnosis of TK2d enables timely therapeutic intervention, which may meaningfully influence clinical outcomes such as prognosis and quality of life.¹

References

1. Habet, 2025. Emerging solutions could make TK2d easier to recognize and treat. https://www.rarediseaseadvisor.com/features/emerging-solutions-could-make-tk2d-more-recognizable-treatable/
2. Rare Disease Advisor, 2025. Thymidine kinase 2 deficiency, Etiology. https://www.rarediseaseadvisor.com/disease-info-pages/thymidine-kinase-2-deficiency-etiology/
3. Berardo, 2022. Advances in thymidine kinase 2 deficiency: Clinical aspects, translational progress, and emerging therapies. https://www.doi.org/10.3233/jnd-210786
4. UCB, 2026. Testing for TK2d. https://www.tk2d.com/testing#:~:text=Genetic%20testing%20is%20the%20only,Hear%20her%20story
5. Rare Disease Advisor, 2025. Thymidine kinase 2 deficiency (TK2d), Treatment. https://www.rarediseaseadvisor.com/disease-info-pages/thymidine-kinase-2-deficiency-treatment/

Developed by EPG Health for Medthority, independently of any sponsor.