Recognising TK2d

Shining a light on TK2d

Thymidine kinase 2 deficiency (TK2d) is a rare, inherited, debilitating, and often fatal myopathic mitochondrial disease, which leads to impaired energy production in cells.^1,2 TK2d is classified as mitochondrial DNA depletion/deletion syndrome, a category of mitochondrial disease.³

TK2d is a primary mitochondrial myopathy that is different from other mitochondrial diseases in that it predominantly manifests as muscle weakness.⁴

This proximal muscle weakness affects different parts of the body. Patients may lose the ability to walk, eat, and breathe independently.^1,4,5

Organ system and related symptoms:^1,3-5

Muscles: Delay, regression, and/or loss of motor milestones, proximal weakness, hypotonia, Gowers' sign, facial diplegia, ptosis^1,3-5 

Respiratory system: Respiratory insufficiency and/or failure due to respiratory muscle weakness^1,3-5  

Gastrointestinal tract: Dysphagia, failure to thrive  

Brain: Some patients may experience central nervous system abnormalities, such as seizures, encephalopathy, and cognitive dysfunction and decline

TK2d has an estimated prevalence of 1.64 cases per million people worldwide.⁶

TK2d is often fatal

When age of symptom onset is 1 year or younger, survival is less than 1 year.^4,5  

TK2d is a deficiency of the thymidine kinase 2 enzyme, which is crucial for the maintenance and synthesis of mitochondrial DNA.^5,7 TK2d is a result of a defect in a nuclear gene (in this case, the TK2 gene), whereas many other mitochondrial diseases are caused by defects in mitochondrial genes.^7,8

TK2d is a progressive disease that can develop at any point in a patient’s life⁴

Early onset of TK2d is related to more severe symptoms with a faster disease progression. Early onset is defined as TK2d symptom onset that occurs before the age of 12 years.⁵ Late onset of TK2d may be possible and is defined as symptom onset after 12 years.^4,5

Because long diagnostic journeys and misdiagnoses are common for patients with mitochondrial diseases, people with TK2d may be diagnosed years after symptom onset. Even those diagnosed as adults may have early-onset TK2d if their symptoms began at or before 12 years of age.^3,7,9

Early onset of TK2d^1,4,5

Onset from 0-12 years

Infants often have a healthy birth and reach early developmental milestones.

Shortly after, they may experience rapid decline characterized by loss of motor milestones and acute respiratory insufficiency.

Infants with symptom onset before age 1 have a median postonset survival of approximately 1 year. Patients with disease onset between ages 1 and 12 years have a median postonset survival to at least 13 years, but this number decreases when onset happens at an earlier age.

Manifestations include facial weakness, droopy eyelids, difficulty eating, trouble breathing, and proximal muscle weakness.^1,4

If left untreated, patients with TK2d have a low chance of survival⁵

Symptoms chart

The clinical manifestation of TK2d is caused by mitochondrial DNA depletions, multiple deletions, or both³

TK2d comprises a clinical continuum of symptoms ranging from slow, debilitating symptoms to rapidly progressive/life-threatening symptoms.^4,5

* These subtypes are a general guide to clinical manifestations; however, each person living with TK2d may present differently. The age thresholds reported are reflective of the scientific opinion of UCB and may differ from those in single publications available in the literature.

TK2d may make my body weaker at certain things, but all that means is that I need different types of support than others.¹

Connie, lives with TK2d

Hear her story

If you suspect TK2d, only certain genetic tests can definitively confirm a diagnosis^1,4

That means some patients may need further genetic testing.¹¹

The TK2 gene is found in the nuclear genome, not the mitochondrial genome.^2,3,12

Because not all tests include the nuclear genome, many do not look for TK2d. Whole-exome sequencing, whole-genome sequencing, and broad genetic panels for nuclear mitochondrial genes usually include TK2.⁴

Order these genetic tests to definitively diagnose TK2d.^1,4

Find out more

TK2d Is Commonly Misdiagnosed^2,6

TK2d shares symptoms with a number of other diseases.^1,3,4

View differential diagnosis

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