Thymidine Kinase 2 Deficiency (TK2d)

Written by Hallie Levine
Medically Reviewed by Neha Pathak, MD on March 21, 2025
13 min read

Thymidine kinase 2 deficiency (TK2d) mainly causes muscle weakness – it’s a very rare mitochondrial disease. Mitochondria are tiny organ-like structures inside your cells that make energy. And if the DNA gets damaged or lost, you can have symptoms.

Genetic changes in your TK2 gene on chromosome 16q21 can come from both parents. The changes stop an enzyme called thymidine kinase from working. It can't repair the DNA inside your mitochondria. 

This mitochondrial DNA (mtDNA) can get lost (mtDNA depletion syndrome) inside your muscle cells over time. You may feel weaker as you get older (progressive muscle weakness), too. It usually affects your muscles (myopathic form), but symptoms can start at different ages (age of onset). There are three main types:

  • Early onset starts in the first year of life.
  • Childhood onset begins between 1 and 12 years old.
  • Late onset begins after 12 years old.

Usually TK2d shows up early, or during childhood. But TK2d is rare and likely not diagnosed at first. Although it’s still unclear, only 600 to 2,700 people have TK2d in the U.S.

TK2D symptoms can depend on when they start, how fast mitochondria lose DNA, and other factors, too. Many doctors group symptoms by your age. There are three general groups for symptoms:

Early-onset TK2d. Babies may grow normally at first. Once the symptoms begin, they’ll likely get symptoms quickly. You may notice that your baby has:

  • Low muscle tone or weakness
  • Trouble feeding
  • A hard time breathing (may need a ventilator)
  • Hearing loss
  • Seizures
  • An eye that droops on one side (ptosis)
  • Problems reaching certain social, mental, or physical milestones (developmental delay)
  • Mental confusion or agitation (encephalopathy)
  • Problems standing up (may use their hands to “walk” up their legs, called Gower sign)

Most infants with TK2d do not learn to walk but can use a wheelchair to get around. Other clinical problems can include heart problems (cardiomyopathy), anemia, or skin problems.

Childhood-onset TK2d. These symptoms progress somewhat rapidly, but slower than infants. The main sign is muscle weakness, in the arms, legs, and face. Your child can have Gower sign – use their hands to “walk” up their legs when standing up. 

You may also notice eye problems like droopy eyelids (ptosis) or trouble moving their eyes. Most kids need a wheelchair by age 10, and eventually, a ventilator. 

A few children also get problems that aren’t muscle related. They can have things like hearing loss, memory loss, or broken bones.

Late-onset TK2d. Signs for TK2d later in your teen years or even adulthood were often present in your childhood. The symptoms were likely mild or went undiagnosed. 

Typically your facial muscles can weaken and your scapula bones stick out. You may also notice that you have: 

  • Weak shoulder, arm, hip, and thigh muscles
  • Drooping eyelids (ptosis)
  • Trouble moving your eyes
  • Difficultly swallowing and talking

Sometimes you may have changes in the sound of your voice (dysphonia) or slurred speech (dysarthria). You can also get problems with your heart, hearing loss, or nerve damage in your hands or feet (peripheral neuropathy). 

With late-onset TK2d, your doctor may talk about devices to help. For example, canes can help you walk around. Or a ventilator may help you breathe easier.

Thymidine kinase 2 (TK2) is a gene on chromosome 16. It's in a certain area on the long arm (q21) of the chromosome. It makes an enzyme (protein), TK2, to repair DNA inside your mitochondria. 

But if you inherit changes in your DNA (mutations) from both parents (recessive), you can get this medical condition. TK2d means "deficiency," the protein can’t repair DNA. 

When the DNA isn't repaired, it can get lost. And over time, mitochondria lose DNA to cause muscle weakness throughout your body.

If you carry just one mutation, you likely won’t show symptoms. But rarely, some people with one DNA change (carriers) have very mild signs for TK2d.

TK2d usually happens when both parents pass down the DNA change. In this case, your baby has a 1 in 2 chance to carry one DNA change. And your baby has a 1 in 4 chance for TK2d.

Your doctor, or your child’s pediatrician, may suspect TK2d if muscle weakness in the arms, legs, and face shows up. But it often comes with respiratory issues and eye problems, too. 

A key sign of mitochondrial disease is symptoms in many different body systems (multisystem involvement). Although you can often get misdiagnosed with other conditions like spinal muscular atrophy (SMA) or muscular dystrophy. 

Some things to look for include rapid muscle weakness that gets worse over time. And other organs and systems affected like eye movement, hearing loss, or breathing problems.

Tests for TK2d

The following tests can help diagnose Tk2d:

  • Blood tests check your liver enzyme levels and a muscle enzyme (creatine kinase) --- high levels may point to TK2d. 
  • Muscle biopsy (a small sample of muscle tissue) checks for abnormal muscle tissues (ragged red fibers), other enzymes, and measures mitochondrial DNA, too.
  • Electromyography (EMG) test measures your muscle function.
  • Genetic tests look for DNA changes to see if you have TK2d.

Since TK2d is so rare, it may not be checked on all gene tests (gene panels). They’ll probably look at your entire gene or all your genes (whole exome or whole genome sequencing). This helps your doctor check large chunks of your DNA. It’s the only way to know for sure.

A diagnosis of TK2d may seem overwhelming or you may have mixed feelings. Talking with your medical team can help you put together the best care plan. Here are some things you can ask during your doctor’s visit:

What is TK2d exactly? They can explain the condition and its symptoms. Your doctor can discuss how TK2d impacts your body.

Does anyone else in my family need to get tested? TK2d is passed down (inherited) from parents to children. So other family members like siblings may want to get tested, too. 

Your doctor can discuss what a carrier is and what that means. Your family may also want to know if they’re carriers. 

What are the treatment options? Treatments for TK2d can help manage your symptoms. Physical and occupational therapy, assistive devices like walkers, and cochlear implants for hearing loss can help.

Are there any clinical trials available for TK2d? Your doctor can direct you to clinical trials in your area. They can help you find resources, too. And they'll answer any questions about clinical trials.

Where can I find support to help manage TK2d? Your doctor can refer you to other specialists. Specialists are doctors that treat a specific area of your body. Your doctor may also suggest seeing physical, occupational, and speech therapists. 

Your doctor can also refer you to organizations and support groups. They can point you to local resources to provide assistance.

TK2d can cause muscle weakness that slowly gets worse over time. To power your muscles, you need mitochondrial DNA --- they create energy. 

Gene changes in your TK2d gene mean you can lose mtDNA from damage. Your mitochondria may not work as well as they should. As the amount of mtDNA goes down over time, your muscles can lose energy.

TK2d usually starts as muscle weakness in your arms and legs. Later, you can have problems with your breathing and eye muscles. The muscles you use to chew, speak, and swallow may also get tired or weak.

This process occurs very rapidly in babies with early-onset TK2d. Most children live a few years. It happens more gradually with childhood-onset TK2d. Many children live till their teen years with TK2d. If TK2d starts late, many adults live about 23 years after their symptoms first appear.

There is no cure for TK2d but treatments can help. Different therapies help stabilize and manage your symptoms. Your medical provider may suggest the following:

Supportive care for TK2d

While there’s no cure, treatments can help make TK2d more manageable. These treatment options include:

  • Adaptive utensils to help make it easier to eat.
  • Back braces to help sit, stand, and walk.
  • Breathing support devices like continuous positive airway pressure (CPAP) and bilevel positive airway pressure (BiPAP) machines.
  • Communication devices like hearing aids or iPads to allow text to speech.
  • Feeding tubes to help you swallow.
  • Orthotics to help you walk.
  • Walkers or wheelchairs to help you move easier.

Experimental therapies for TK2d

Experimental therapies have not been approved yet. The medicines are still being studied for TK2d to see if they work. 

Nucleoside therapy for TK2d. This therapy is still being studied for TK2d in clinical trials. The treatment supplies nucleosides for your body. Nucleosides are the building blocks of DNA. Studies report it may help mitochondrial DNA renew and stay strong. 

Research suggests early nucleoside treatment can stop TK2d from getting worse in kids with early-onset disease. During one study, treatment helped a few get off ventilators and allowed two children to walk. This therapy may also help adults but the studies weren't clear. So researchers continue to test this medicine.

Another nucleoside therapy, called MT1621 (Zogenix), is being studied in clinical trials. Researchers hope it helps mtDNA and cell function. Although not FDA approved, you may be able to get it in a clinical trial.

Some doctors also prescribe nucleoside therapy through the FDA compassionate use program. Ask your doctor if you’re a good fit for this treatment.

Gene therapy. This treatment isn't available and is being studied for TK2d. The goal is to replace your TK2 gene changes with new (functional) copies. Although studies suggest it's successful in mice, gene therapy hasn’t been done in humans.

Here are some of the health care providers you’re likely to work with for your TK2d:

  • A pulmonologist and possibly a respiratory therapist to help with your breathing problems.
  • A cardiologist to monitor your heart muscle.
  • A GI doctor and perhaps nutritionist to help with feeding problems to ensure good nutrition.
  • Physical therapist to help keep your muscles strong.
  • Occupational therapist to help with activities of daily living.
  • Pediatrician or primary care doctor to manage your overall health and regular wellness checkups.
  • Geneticist for testing and a genetic counselor to helps answer questions.
  • Neurologist to help with movement-related challenges.
  • Speech therapists to help with speech and chewing.

The main problems (complications) for TK2d happen slowly, over time (progressive). Your muscle weakness may get worse as you get older. Or it can be mild. And your symptoms may make it harder or even impossible to walk, eat, or breathe. 

In time, your lungs may not get enough oxygen (respiratory failure). Or a group of life-threatening symptoms may develop. But it can depend on your type of TK2d, too.

Early onset symptoms that can cause problems may include:

  • Brain inflammation (encephalitis)
  • Mental or developmental delay (cognitive)
  • Hearing loss
  • Seizures

Childhood onset TK2d symptoms can cause problems like:

  • Facial paralysis
  • Droopy eyelids
  • Trouble moving the eyes

Late-onset TK2d can lead to problems such as:

  • Scapular winging (shoulder blades weaken and your blades can stick out)
  • Droopy eyelids
  • Trouble moving your eyes

Because TK2d usually progresses with time, your muscles may also get weaker, too. You’ll likely have muscle weakness near the center of your body. Over time, you may lose your ability to walk, eat, or breathe on your own. But everyone is unique, and TK2d can happen differently in each person.

Most people with TK2d benefit from a wide range of therapies. Although there isn’t a cure, these therapies can help some symptoms. 

These include physical, occupational, speech, and respiratory therapy. Therapists can help you keep your muscles strong. They’ll show you how to use your muscles the best way. And the exercises can maximize your quality of life. 

A nutritionist may also help. They'll make sure you get the nutrients your body needs. Certain supplements may also be doctor-recommended. The goal is to manage symptoms, slow your disease, and its impact.

While living with TK2d can be challenging, there are things you can do to make things easier. Here are a few things that may help:

Working with a gastric tube. If your muscles become too weak to chew, a feeding tube may help. It can put food, fluids, and medications in your body. The food is a formula mixed with proteins, carbohydrates, fats, vitamins, and minerals.

Your doctor’s office can work with you to show you how to use it. Don’t mix liquid formula with medication, though. It can clog your feeding tube.

It’s also very important to flush your tube with warm water before and after you use it. Use a syringe to push water through the tube. You should also clean the opening of it with an antiseptic wipe each day. This can help keep it clean.

Speech therapy. A speech and language therapist can help you strengthen your mouth muscles. Stronger muscles help make it easier for you to talk and chew.

They may also suggest diet changes to help you get enough calories and keep hydrated. If it’s too hard to talk, they can teach you how to use a communication device like a talker.

Respiratory therapy. These therapists work with you to keep your breathing (respiratory) muscles strong. They’ll help make it easier for you to breathe, too. If you need a breathing device like a CPAP, they’ll show you how to use it. 

If your respiratory muscles get weaker, it can be harder to cough out lung mucus. They can teach you chest exercises to help loosen and remove your lung secretions. 

Physical and occupational therapy. A physical therapist can help strengthen any weak muscles. They’ll help you maintain your strong muscles, too. The goal is to prevent losing your strength (deconditioning). This may worsen your TK2d. 

One good option is aquatic therapy – water sports. Since your body is supported in the water, there’s less strain on your muscles and joints. It’s also a good muscle workout. An occupational therapist can suggest daily activity changes so you can keep eating, dressing, and bathing yourself.

Diet modifications. It’s very important to get protein and complex carbohydrates in every meal and snack. Protein can help you keep up your muscle mass and the carbohydrates convert into energy. 

In general, you'll likely have four to six small meals and snacks a day. Talk to your doctor about the best meal plan for your health. It’s also a good idea to have supplements handy, like Ensure. 

Mitochondrial cocktails. There are many vitamins and supplements suggested for people with a mitochondrial disease such as TK2d. Some of the nutrients you use may need a compounding pharmacist to create — a “cocktail” containing certain doctor-prescribed ingredients. 

Some common nutrients your doctor may recommend include coenzyme Q10, B vitamins, and antioxidants. The antioxidants can include alpha lipoic acid, vitamin C, and L-carnitine. Always check with your doctor before taking any supplements or medications.

If you're the parent of a child who has TK2d, it can impact every aspect of your life. To advocate for your child, you may need to create some time for yourself. Even a small daily action can go a long way to help you recharge. Here’s what you can do:

Focus on the basics. Make sure to get enough sleep. Eat healthy foods, exercise regularly, and stay hydrated. All these actions can help give you the physical and emotional strength you need to advocate for your child. 

Follow a script. It can also help to have a few rehearsed “scripts” ready whenever you’re in a stressful moment. These can be simple, like reminding yourself that you’re a good parent. 

Or tell yourself that you’re doing your best or that you need to slow down. Try to take five deep breaths before you respond to a situation. 

Do a daily self-care moment. Take at least 5 to 10 minutes a day --- do something good for yourself. Consider it a daily self-care snack. Some options include:

  • Use a meditation app like Calm or Headspace for a quick mindfulness or meditation exercise. 
  • Call a loved one for a quick hello.
  • Listen to a favorite song. 
  • Read a few pages of a book you enjoy.
  • Play a quick game on your iPhone.

Manage social media. Social media can be a great way to connect with other TK2d families. But it may also make you feel like you’re on overload. So try to set a daily time limit. 

Instead, use that extra time to check in via a phone call or text to people who care about you.

Where to find support

You can always find resources about TK2d and connect with families at websites like MitoAction, CureMito, or take on TK2d. The United Mitochondrial Disease Foundation is another great place to connect and find support, too.

Thymidine kinase 2 deficiency can start in the first year of life (early onset), between 1 and 12 years old (childhood onset), or later (late onset). Early-onset TK2d weakens the muscles, especially your breathing. After a few years, children may have life-threatening respiratory failure.

With childhood-onset, TK2d goes slower and many children live into their teens. But life-threatening respiratory failure may still occur. Teens and adults diagnosed with late-onset typically live up to 23 years after symptoms begin.

Thymidine Kinase 2 deficiency is a very rare mitochondrial medical condition. Changes to the TDK gene on chromosome 16q21 can cause life-threatening muscle weakness that slowly worsens. While there is no cure, treatments can help manage your symptoms. Physical, occupational, speech, and respiratory therapy can help you walk, speak, eat, and eventually breathe with assistance.

What are the symptoms of mitochondrial damage? 

Signs of mitochondrial damage include muscle weaknesses, poor growth, poor vision, and hearing loss. Developmental delay, seizures, migraine, and life-threatening breathing problems are common, too. They can start at birth or at any time.

Can you develop mitochondrial disease like TK2d later in life? 

You can develop mitochondrial disease like TK2d at any point in your life. If you have TK2d, the earlier your diagnosis, oftentimes the more serious your symptoms. And the faster the disease may progress.

What are nutraceuticals or mito cocktails for TK2d? 

Mito cocktail is a nickname for nutraceuticals. This refers to supplements that some doctors may recommend for your TK2d. 

Some of the most common ones include coenzyme Q10, B vitamins, L-carnitine, creatine, and alpha lipoic acid.  Always talk to your doctor before trying any supplement, including nutraceuticals.

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