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 

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.