We’re making progress, but there’s a lot left to do.


Thymidine kinase 2 deficiency, or TK2 deficiency (TK2d), is a very rare genetic disease with about 100 known patients. It is also called Thymidine kinase 2–related mitochondrial DNA depletion syndrome.

  • TK2d was first diagnosed in children in 2001
  • It was just in 2013 that improved genetic testing discovered an adult form of TK2d

Because the genetic testing that finds TK2d is so new, and there are many other mitochondrial depletion syndromes (MDS) with symptoms like those of TK2d, it is believed that there are many more people who have TK2 who have not been diagnosed.

Let’s work together

Whether you’re living with an MDS, have been identified with TK2d, or are a parent, caregiver, or HCP who wants to learn more about MDS and TK2d, join the registry so we can all take on TK2d together.


Patients and caregivers, continue reading. HCPs, learn more HERE.



An introduction to mitochondrial diseases


Inside each of our cells are mitochondria, or the powerhouses of the cell. Their job is to make the energy the body needs to function properly, including actions like lifting your arm or inflating your lungs with each breath. This energy is referred to as adenosine triphosphate, or ATP. 


You may have heard of DNA before and know that it’s stored inside the nucleus of our cells. That is called nuclear DNA. But did you know that we also have mitochondrial DNA (mtDNA)?

To make ATP, the mitochondria need enzymes and proteins from both our nuclear DNA and our mtDNA. When there is an error, or mutation, in either kind of DNA, this mutation can cause a mitochondrial disease. Ultimately, mitochondrial diseases result in less ATP being made than the body needs to work right. 

There are many kinds of mitochondrial disease that affect people in very different ways. In fact, 2 people with the same mutation may experience their disease completely differently. This is one of the reasons it is difficult to diagnose mitochondrial diseases or predict how a person may experience it. Mitochondrial diseases may affect the brain, heart, muscles, eyes, gastrointestinal tract, and many other systems. 

One class of mitochondrial diseases is mitochondrial DNA depletion syndromes (MDS or MDDS). Many people have a diagnosis of MDS, but getting a specific genetic diagnosis—like TK2d—is hard. 


With MDS, your cells are not making enough mtDNA to create ATP. There are many MDS disorders, and TK2d is one of them, primarily affecting muscles, including those that impact the function of the lungs and eyes. 


TK2 deficiency basics


TK2d is an enzyme deficiency. It is a genetic disease that is defined by muscle weakness (myopathy), with effects like difficulty breathing, droopy or saggy eyelids, or trouble chewing and swallowing. It can take a long time before a person is diagnosed with  TK2d. Why? Because TK2d is such a rare disease, doctors are just beginning to learn about it. Also, muscle weakness is a sign of many diseases, so there are many disorders for doctors to think about and check for.


What does the TK2 gene do?


Simply put, a fully functional TK2 gene is needed for normal function of mtDNA. Fully supported mtDNA is necessary for proper cell function.


What happens with TK2d?


With TK2d, less mtDNA is being made. The result is lower ATP production, which means muscles don’t have enough energy and cannot function right. The more mtDNA depletion you have, the worse your TK2d will be.


Genetics and inheritance


TK2d is a very rare inherited genetic disease. To have TK2d, both your mother and your father must be carriers of mutated (or altered) copies of the TK2 gene and pass those mutated genes to you. This is called autosomal recessive inheritance.


Types and symptoms of TK2d


There have been many genetic alterations (or changes) found in the TK2 gene that can lead to someone having TK2d. The type of gene a person inherits can predict how severe their TK2d can be and when it may show up. There are 2 types of TK2d: infantile/childhood onset and adult onset.


Infantile/childhood onset


This type of TK2d represents around 80% of cases.

TK2d may start as early as the first year of life through the early teenage years. The infantile/childhood form of TK2d is the most severe and often gets worse very fast. The earlier in life symptoms start, the quicker symptoms progress.


Symptoms may include: 

  • Muscle weakness that gets worse over time
  • Low muscle tone (hypotonia—also called floppy baby syndrome)
  • Trouble breathing
  • Problems chewing and swallowing
  • Loss of motor skills (like crawling, walking, balancing, and grabbing)
  • Poor reflexes
  • Neurological effects, such as seizures or altered brain activity and function
  • Slowed mental development
  • Hearing loss

When showing up in older children, TK2d develops more slowly and may also include more symptoms, such as:

  • Droopy eyelids (ptosis)
  • The inability to move the eyes and eyebrows (progressive external ophthalmoplegia, or PEO)

Adult onset


This type represents around 20% of cases.

With this type, TK2d starts in the teenage years through adulthood. The first signs might be when you notice it’s hard to do simple tasks (like climbing stairs) or have shortness of breath. Many people, once diagnosed, look back and realize that there were symptoms earlier in their lives that could be explained by having TK2d. Adult-onset TK2d is still severe, but progression is slower and more varied.

Symptoms may include:

  • Muscle weakness
  • Difficulty breathing
  • Droopy Eyelids (ptosis)
  • The inability to move the eyes and eyebrows (progressive external ophthalmoplegia, or PEO) 
  • Trouble swallowing (dysphagia)

The path to diagnosis


In general, mitochondrial diseases are hard to diagnose because the symptoms look like those of other conditions. For example, symptoms of spinal muscle atrophy (SMA) are a lot like those of TK2d. Because of this, patients are often misdiagnosed.

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If a doctor thinks someone may have TK2d, he or she will administer a combination of blood tests, muscle biopsies, and genetic tests to search for a diagnosis. Lab tests look for levels of creatine kinase (CK) and lactic acidosis in the blood. Special attention will be paid to the progression of muscle weakness, elevated serum CK levels, and lactic acidosis. Doctors may also do a muscle biopsy to look at ragged red fibers, check levels of certain enzymes, and measure mtDNA levels. Electromyography (EMG) tests may also be performed to look at muscle function. 

The only way to confirm a diagnosis of TK2d is through genetic testing. 

Because we are in the early stages of learning about TK2d, we need to grow our community so we can further all the efforts being made to improve diagnosis and potential treatments for TK2d. Please help us by joining our registry.




There are no FDA-approved medicines to treat TK2d. Treatment is focused on managing the symptoms a patient experiences. Your treatment team will include doctors from different specialties. For example, a pulmonologist will help manage lung function and breathing. Physical therapists or rehabilitation specialists will help with muscle function and movement. Your primary doctor will likely be a neurologist or a doctor who specializes in metabolic disorders.


Moving forward


There is still much to be learned about living with TK2d. As awareness and knowledge of TK2d increases, our understanding of the disease and the experiences of patients will too. 

You can help! We want to get to know you and how you take on TK2d. Please join the registry and help us by growing the community and letting our collective experience be the driving force behind change. Join us!



Here are links to patient advocacy groups and sites that have information about TK2d.

United Mitochondrial Disease Foundation

UMDF is dedicated to promoting research and education for the diagnosis, treatment, and cure of mitochondrial disorders and to provide support to affected individuals and families.

Muscular Dystrophy Association

The MDA is dedicated to transforming the lives of people affected by neuromuscular disease.

Mitochondrial Disease Action Committee 

This nonprofit organization was founded by patients, parents, and Boston hospital healthcare leaders who had a vision of improving quality of life for children and adults with mitochondrial disease.

International Mito-Patients

Powerful patient organizations from different countries in the world have joined forces in their fight to be a voice on an international level and find a cure for mitochondrial disease.

NAMDC (North American Mitochondrial Disease Consortium)

This site provides resources and information for patients and caregivers about mitochondrial disease, including a list of open studies for patients and a list of participating clinical centers.  

Genetics Home Reference
National Institutes of Health, US National Library of Medicine

This resource provides consumer-friendly information about the effects of genetic variation on human health.

Mitochondrial Myopathies Information Page
National Institutes of Health, National Institute of Neurological Disorders and Stroke
This site provides information about research, treatment, and patient organizations for mitochondrial myopathies.


Glossaries of medical terms
Here are sites that can help you understand medical terms.

Talking Glossary of Genetic Terms

This source was created to help everyone understand the terms and concepts used in genetic research. Many definitions include images, animations, and links to related terms.

National Society of Genetic Counselors Glossary

This is a genetics-based glossary.

What Did My Doctor Say?

This site aims to help health consumers and patients understand “medspeak.”