TK2d Basics

Thymidine Kinase 2 deficiency (TK2d) is an ultra-rare genetic disease characterized by progressive muscle weakness.

Read on to find answers to some of the most frequently asked questions about TK2d.

What causes TK2d?

TK2d is caused by a mutation or change in the TK2 gene. This causes cells to be unable to make enough of the functional TK2 enzyme.

The role of this enzyme is to recycle mitochondrial DNA, so when there is a shortage of TK2 enzyme, mitochondrial DNA maintenance and replication are impaired. This, in turn, results in a drop in the number of mitochondria in cells. 

Since mitochondria are essential for energy production, a drop in their number means not enough energy is being made. Because muscle cells require a lot of energy to function, the main symptom of TK2d is muscle weakness.

How common is TK2d?

TK2d is an ultra-rare disease, meaning it affects fewer than one in 50,000 people.

It is estimated that the worldwide prevalence of TK2d is 1.64 cases per 1 million people, and it affects approximately 600 to 2,700 people in the U.S.

How do doctors diagnose TK2d?

There are several tests that a doctor can use to diagnose TK2d. These include blood tests, electromyography, muscle biopsy and brain imaging tests. A definite diagnosis can be reached following a genetic test.

If I have a child with TK2d, will my other children also have it?

TK2d is inherited in an autosomal recessive manner. This means that a patient must have two copies of the faulty gene to develop the disease.

If you already have a child with TK2d, it means that both you and your partner are carriers of the disease, or have one faulty copy of the TK2 gene. This means that you have a 25% risk of having another child with the disease. 

What is the life expectancy of a patient with TK2d?

Life expectancy depends on the type of TK2d a patient has.

In its most severe infantile-onset form, the life expectancy of TK2d is only one to two years from the time of symptom onset. Patients with childhood-onset TK2d, or those in whom the symptoms appear between ages 1 and 12, usually live to their teenage years.

A patient with late-onset TK2d, whose symptoms appear after age 12, has a life expectancy of 20 to 30 years from the time of symptom onset. 

Are there any treatments for TK2d?

The U.S. Food and Drug Administration approved Kygevvi (doxecitine and doxribtimine) powder, the first drug approved to treat TK2d, in November 2025. Researchers are also studying the use of gene therapy alone and in combination with nucleoside therapy to treat TK2d.

Kygevvi is expected to be commercially available in the US in the first quarter of 2026. 

There are also treatments like physiotherapy that can help maintain muscle strength. Assistive therapies such as ventilatory care and feeding support can help improve patients’ quality of life.

Supportive treatments, like a gastrostomy tube for feeding difficulties, non-invasive or invasive ventilators for respiratory problems, cochlear implants for hearing loss, and anti-epileptic medications for seizures, can help address the manifestations of TK2d.

Are there any new treatments in development?

Another potential therapeutic approach for TK2d is gene therapy. 

This approach makes use of viral vectors or “vessels” to deliver a healthy copy of the gene that codes for the TK2 enzyme to the body. The aim is to ensure cells make enough functional TK2 enzyme by themselves, thereby addressing the root cause of the disease.

This approach has been successfully tested in animal models of the disease, which showed that enzyme activity was restored in most tissues and the progression of the disease was delayed.

A combination approach of gene therapy and nucleoside therapy has also shown promise in preclinical studies with improved outcomes, including better physical growth and overall survival. This approach may be the way forward for the treatment of TK2d in the future.