Thymidine Kinase-2 Deficiency (TK2d)

A common symptom of TK2d is myopathy. Myopathy means muscle disease.

In TK2d, myopathy can cause:

• muscle weakness, often in the arms, legs, neck or trunk
• tiredness or reduced stamina during physical activity (exercise intolerance)
• difficulty walking, running, climbing stairs or lifting objects
• shortness of breath during activity
• breathing difficulties caused by weak breathing muscles (respiratory muscle weakness)
• swallowing or feeding difficulties (dysphagia)
• speech difficulties caused by weak mouth and throat muscles (dysarthria)
• facial weakness, sometimes affecting both sides of the face (facial diplegia).

Other symptoms may include:

• low muscle tone (hypotonia)
• delayed physical development or loss of physical skills (developmental delay or motor regression)
• seizures
• hearing loss
• poor growth or poor weight gain in babies and young children (failure to thrive)
• drooping eyelids (ptosis)
• difficulty moving the eyes (ophthalmoplegia)
• heart muscle disease (cardiomyopathy).

For more information

Understand the signs and symptoms of mito

TK2d is a genetic condition. This means it is caused by changes in a person’s DNA.

TK2d is caused by changes in the TK2 gene. The TK2 gene is part of a person’s nuclear DNA. Nuclear DNA is the DNA stored in the centre of most cells.

What happens in the body

The body needs energy for everything it does, including moving, breathing, growing and sleeping. 

This energy is made by mitochondria. Mitochondria are tiny parts inside cells that help turn food and oxygen into energy. 

Mitochondria also have their own DNA, called mitochondrial DNA (mtDNA). They need mtDNA to help make energy for the body’s cells. 

The TK2 gene helps the body make an enzyme called thymidine kinase 2. This enzyme helps mitochondria maintain and repair their mtDNA. 

In TK2d, changes in the TK2 gene mean the body does not make enough working thymidine kinase 2 enzyme. 

Without enough working enzyme, the amount of mtDNA can become reduced. This is called mitochondrial DNA depletion, or mtDNA depletion. 

When mitochondria do not have enough mtDNA, they cannot make energy as well as they should. This particularly affects muscles, because muscles need a lot of energy to work. 

This helps explain why TK2d often causes muscle symptoms, such as muscle weakness, breathing muscle weakness, swallowing difficulties and movement difficulties. 

Inheritance

Everyone has 2 copies of the TK2 gene.  

A person usually has TK2d when both copies of their TK2 gene have changes that affect how the gene works. The 2 gene changes do not need to be the same. A person can have 2 different TK2 gene changes and still have TK2d. 

TK2d is usually passed down in an autosomal recessive way. This means a child usually needs to inherit one changed TK2 gene from each biological parent to have TK2d. A person with one changed copy of the TK2 gene is called a carrier. Carriers usually do not have symptoms of TK2d. 

When both biological parents are carriers, each pregnancy has: 

• a 25% chance the child will have TK2d
• a 50% chance the child will be a carrier
• a 25% chance the child will inherit two working copies of the TK2 gene, hence the child will be unaffected.

If only one biological parent is a carrier, and the other parent has 2 working copies of the TK2 gene, their children will not usually have TK2d. Each child has a 50% chance of being a carrier. The chance is the same whichever biological parent is the carrier. 

Because carriers usually do not have symptoms, TK2d can happen in a family with no known history of the condition. 

Variation between people

Symptoms and how serious they are can vary from person to person. This can happen even within the same family.

Some people have symptoms in infancy or childhood. Others develop symptoms later in life.

The type of TK2 gene change does not always predict how severe TK2d will be.

Understanding family planning options

Some people with TK2d, or with a family history of TK2d, may choose to learn more about the chance of passing on a TK2 gene change. 

Some people choose to explore family planning options with support from a genetic counsellor or clinical genetics service. This can help people understand their genetic information, the chance of passing on a gene change, and the reproductive options that may be available to them. 

Options may include natural conception with or without prenatal testing, in vitro fertilisation (IVF) with genetic testing, using donor eggs, donor sperm or donor embryos, adoption, or choosing not to have children. 

These decisions are personal. They may depend on a person’s values, circumstances, health, family situation and preferences. 

Genetic counselling can help people understand what these options may mean for their family. Mito Foundation’s Options for building your family resource has more information.

This section combines information from trusted sources.^3,4,6,8,9 The explanations have been adapted into plain language by Mito Foundation. 

For more information

Learn more about genetics and mito

Information to understand your diagnosis

Information to understand your child’s diagnosis

Diagnosing TK2d usually involves looking at a person’s symptoms, medical history, family history, physical examination and test results.

A health professional may suspect TK2d when a person has progressive muscle weakness, especially if the breathing muscles are affected. Progressive means that change happens gradually over a period of time.

Swallowing, feeding, movement or eye muscle symptoms may also suggest TK2d.

Testing may look at how TK2d is affecting the muscles, breathing and other body systems. It may also help rule out other conditions with similar symptoms.

Tests may include:

• blood tests, which may check creatine kinase (CK), lactate and other markers that can be linked to muscle or mitochondrial changes 

• breathing tests, which check how well the breathing muscles and lungs are working 

• electromyography (EMG), which checks how the muscles respond to nerve signals 

• muscle magnetic resonance imaging (MRI), which can show patterns of muscle changes 

• muscle biopsy, which looks at a small sample of muscle under a microscope 

• genetic testing, which looks for changes in the TK2 gene.

Genetic testing

If TK2d is suspected, a health professional may arrange genetic testing. Genetic testing looks for changes in a person’s DNA, including changes in the TK2 gene. 

Genetic testing often uses a blood or saliva sample. In some cases, another type of sample may be needed. 

A gene panel needs to include the TK2 gene for TK2d to be detected. If TK2 is not included, a diagnosis may be missed. 

Genetic testing is specialised, and results can take time. In some cases, the results may not give a clear answer. This can happen if a gene change is not found, or if the meaning of a gene change is not yet fully understood. 

Genetic counsellors can support people and families before or after genetic testing. They can help explain results and what those results may mean for the person and their family. 

This section combines information from trusted sources.^2–4,10,11 The explanations have been adapted into plain language by Mito Foundation. 

For more information

Learn more about genetics and mito

Doxecitine and doxribtimine (Kygevvi®) is a medicine approved in some countries for some people with TK2d.^12,13

This medicine may be named in different ways:  

Active ingredient: doxecitine and doxribtimine. 

Brand name: Kygevvi®  

Other names used in research: deoxynucleoside therapy, pyrimidine nucleoside therapy, or dC and dT therapy.⁴

The active ingredient is the name of the medicine itself. The brand name is the name used by the company that makes it. Some research may use other names. 

Currently as of July 2026, doxecitine and doxribtimine (Kygevvi®) is not approved by the Therapeutic Goods Administration (TGA) in Australia.¹⁴ The TGA is the Australian Government agency that checks medicines for safety, quality and effectiveness before they can be supplied in Australia through the usual approval pathway. 

This information can change over time. The Mito Foundation doxecitine and doxribtimine (Kygevvi®) page has more updated information about: 

• whether doxecitine and doxribtimine (Kygevvi®) is approved in Australia 

• who it may be relevant for 

• what research has been done 

• what is still unknown 

• possible risks and side effects 

• clinical study information. 

Read Mito Foundation’s doxecitine and doxribtimine (Kygevvi®) page. 

TK2d is a serious condition that can shorten life expectancy.^3,4 How TK2d affects life expectancy can vary from person to person. 

The age when symptoms first appear is one of the main factors linked to severity and survival.³

Babies who develop symptoms in the first year of life can have complex health challenges. Infantile-onset TK2d is linked with a higher risk of early death, often because the breathing muscles become severely affected.^3,4 

Childhood-onset and late-onset TK2d can also affect life expectancy, but survival is more varied. Published studies show that survival after symptoms begin can differ widely between people.³  

This information can be difficult to read and process. Every person’s experience of TK2d is different. A health professional can help explain what this information may mean and what monitoring or support may be appropriate over time. 

Mito Foundation provides information to help people affected by mito understand clinical trials and how to find opportunities that may be relevant to them.

Clinical trials help researchers test new ways to prevent, diagnose, treat and manage mito. Some trials test whether a treatment is safe and whether it may help people.

Other clinical studies may look at symptoms, diagnosis, genetics, quality of life, or how mito affects people over time.

Clinical trials are carefully planned. The therapies being studied may be at different stages. Trials may not be available for every type of mito, and not every trial will be right for you. Some trials are only open to people with a confirmed genetic diagnosis, specific symptoms, a certain age range, or the ability to attend study appointments.

Mito Foundation’s emerging therapies information explains therapies in development, how clinical trials work, and what you may wish to consider before taking part. You can also use the Therapy Finder to explore therapies in development and see what may be relevant to you.

Learn more about taking part in clinical trials       Use the Therapy Finder

Staying informed

One way to hear about opportunities to take part in clinical trials is to join the Mito Registry.

The Mito Registry helps connect people with research opportunities that may be relevant to them. It also helps Mito Foundation understand how many people in Australia are affected by different types of mito.

This information can help support future research, services and advocacy.

Join the Mito Registry

International mito patients (imp): Take on TK2d 

Take on TK2d: TK2d  

National Organisation for Rare Disorders: TK2d 

Genetic and Rare Diseases Information Centre: Mitochondrial DNA depletion syndrome, myopathic form

Mito Support Community – Facebook group 

As of July 2026, no active support groups dedicated to TK2d were found.