Join us, and together we’ll take on TK2 deficiency.

 

Thymidine kinase 2 deficiency, TK2 deficiency (TK2d), is a very rare genetic disease. Tk2d is a form of mitochondrial DNA depletion syndrome.

  • 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 mitochondrial depletion syndromes (MDS) with symptoms like those of TK2d, it is thought that there are many more people with TK2d who have not been diagnosed.

Let’s work together

Whether you’re living with an MDS, have been diagnosed with TK2d, or are a parent, caregiver, or healthcare professional (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.

 
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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. 

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

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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. 

 
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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?

 
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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 may be.

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Genetics and Inheritance

 

TK2d is a very rare inherited genetic disease. To have TK2d, both your mother and 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.

 
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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 may or may not predict how severe their TK2d can be and when it may show up. TK2d can either present during infancy/childhood or in adulthood.

 

Infantile/childhood onset

 
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Around 80% of TK2d patients have onset in childhood.  

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. Generally, the earlier in life symptoms start, the quicker symptoms progress.

 
 
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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

 
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This type represents around 20% of cases.

TK2d can also start 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

  • Fatigue

  • Difficulty walking

  • Difficulty breathing

  • Droopy eyelids (ptosis)

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

  • Trouble swallowing (dysphagia)

  

 
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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. 

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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.

 
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Management

 

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.

 
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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!
 

 
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Resources

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

Glossaries of medical terms

Here are sites that can help you understand medical terms.