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TK2d

If you're just learning about TK2d, you may be feeling overwhelmed and unsure of the future. You probably have lots of questions, and genetic testing may give you some answers.

Genetic testing is the most direct way to find out if you have TK2d. Early genetic testing can confirm a diagnosis, help patients seek the care they need, and allow them to enroll in available clinical trials.

my gatsby image

If you're just learning about TK2d, you may be feeling overwhelmed and unsure of the future. You probably have lots of questions, and genetic testing may give you some ansers.

Genetic testing is the most direct way to find out if you have TK2d. Early genetic testing can confirm a diagnosis, help patients seek the care they need, and allow them to enroll in available clinical trials.

What is TK2d?

Thymidine kinase 2 deficiency (TK2d) is a rare genetic mitochondrial disease

TK2d is a genetic mitochondrial disease that can have a serious impact on a person's health and quality of life. To best understand TK2d, there are some things about the body that you need to know first.

Mitochondria and ATP

Inside each of our cells are mitochondria, the powerhouse of the cells. Their job is to make the energy that is essential to many critical body functions, like lifting your arm or inflating your lungs with each breath. This energy is called adenosine triphosphate, or ATP. 

DNA and mtDNA

You may know that some DNA is stored inside the nucleus of our cells (called nuclear DNA), but did you know that we also have mitochondrial DNA (mtDNA)? This mtDNA plays an important role in creating ATP.

Mitochondrial disorders

To make ATP, the mitochondria need enzymes and proteins from both our nuclear DNA and our mtDNA. When there is an error (mutation) in either type of DNA, it can cause a mitochondrial disorder. An estimated 1 in 5,000 adults has a mitochondrial disorder.

Understanding TK2d

TK2d is a myopathic form of mitochondrial disease, meaning it affects muscles. It is also a type of mitochondrial disease called mtDNA depletion syndrome (MDS or MDDS).

Thymidine kinase 2 (TK2) is an enzyme that helps make and maintain your mtDNA. When you have a healthy and normal amount of mtDNA, the mitochondria are able to create and provide energy for your body and its functions.

TK2d is an enzyme deficiency, meaning there are not enough TK2 enzymes available to help make and repair your mtDNA. Because there isn’t enough healthy mtDNA, the mitochondria cannot work the way they should. This means muscles don’t have enough energy and cannot function properly. This can lead to weakness in many muscle groups.

Illustration of TK2 enzyme with and without TK2d

quick facts

  • TK2d was first diagnosed in children in 2001
  • In 2013, improved genetic testing led to the discovery of an adult form of TK2d

Because the genetic testing that finds TK2d is so new, and there are many other diseases with symptoms like those of TK2d, it is thought that there are many more people with TK2d who have not been properly diagnosed.

What are the symptoms of TK2d?

TK2d is defined by severe muscle weakness (called myopathy) and can affect life in a range of ways. Many patients lose the ability to walk, eat, and breathe independently. Tragically, it is also often life-threatening.

Because TK2d is a disease with many symptoms, diagnosing TK2d can be a long journey. It can take multiple visits to health care providers to get a confirmed TK2d diagnosis.

However, if you suspect TK2d, genetic testing is the most direct path to a diagnosis.

TK2d causes a spectrum of symptoms that can impact people of all ages

Symptoms can progress slowly or quickly, depending on the patient and age of onset. Generally, the earlier in life symptoms start, the more severe they are and the quicker they progress.

Symptoms of

Early onset

TK2d

Young children often have a healthy birth and reach early developmental milestones. Shortly after, they may experience:

baby
Serious respiratory issues
(trouble breathing)
Low muscle tone
(hypotonia, also called floppy baby syndrome)
Loss of motor skills
(like crawling, walking, balancing, and grabbing)

Symptoms of

Late onset

TK2d

Teens and adults often have less severe symptoms that do not progress as quickly as early onset TK2d, including:

Teens and adults often have less severe symptoms that do not progress as quickly as early onset TK2d, including:

Facial weakness
Difficulty eating
Shortness of breath
Droopy eyelids or inability to move eyes/eyebrows (progressive external ophthalmoplegia)
Fatigue and weakness of upper arm and shoulder
Early onset is defined as ages of 0-12 years old; late onset is defined as > 12 years old.

Getting a diagnosis

If you or a loved one has several of the symptoms listed above and you suspect TK2d, there are no-cost genetic testing options to help with a diagnosis. And with each new diagnosis, we can discover more about TK2d.

What causes TK2d?

Symptoms of TK2d begin to appear early in life for many patients, but TK2d can sometimes develop in teens and adults, too.

TK2d is an inherited disease caused by a genetic mutation in the TK2 gene. Both the mother and father (called “carriers”) must have a copy of the altered TK2 gene for a child to get TK2d. This is called an autosomal recessive inheritance pattern.

When both parents are carriers of the TK2 gene, each child will have a 25% chance of having TK2d, a 50% chance of being an unaffected carrier, and a 25% chance of not having TK2d and not being a carrier.


The mother and father who pass on TK2d will usually not have any signs or symptoms of the disease. That is one reason why getting a diagnosis can be hard for someone who inherits TK2d.

If you or a loved one has been diagnosed with TK2d, you should also talk to your doctor about how to learn if siblings or other family members may be carriers.

White half
Normal Gene
Yellow half
Mutated Gene
Carrier parents
Carrier DadCarrier Mom

These are the possibilities with two carrier parents:

baby

25%

Chance of having TK2d
baby

50%

Chance of being an unaffected carrier of a single mutatedTK2 gene
baby

25%

Chance of not having TK2d and not being a carrier

How is TK2d managed?

While TK2d can often have serious or even life-threatening consequences, there are several ways that doctors can help manage the symptoms of TK2d to try to limit its impact. They may use medical equipment and therapies such as:

  • Respiratory support/therapy
  • Feeding tubes
  • Wheelchairs
  • Physical therapy
  • Nutraceuticals (sometimes called a "mito cocktail")

Caring for someone with TK2d usually involves a multidisciplinary team that includes a physical therapist to help keep muscles functioning and other specialists as needed (eg, a pulmonologist to manage breathing problems). A multidisciplinary team may include:

  • Neurologists
  • Pulmonologists
  • Metabolic specialists
  • Gastroenterologists
  • Physical therapists
  • Speech therapists
  • Clinical genetics
  • Genetic counselors

While there are no FDA-approved therapies to treat TK2d, we continue to learn more about the disease and potential treatments

Illustration of parents pushing child in stroller
Several clinical trial programs are currently being conducted for different mitochondrial diseases, including TK2d. These studies help advance our knowledge and provide hope for the community.
So, while there are still many questions, clinical trials and genetic testing can help guide the community and will help us all take on TK2d!

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