TK2d Basics

Thymidine kinase 2 deficiency (TK2d) is an ultra-rare genetic disease that can be challenging to diagnose. 

There are several tests doctors may perform to reach a diagnosis, including a physical examination and a complete medical history of the patient, blood tests, an electromyography, a muscle biopsy, brain imaging tests and genetic tests.

Physical examination and medical history

TK2d diagnosis often starts with conducting a physical examination and gathering all known medical history of the patient. 

The doctor will examine the patient and look for signs and symptoms of the disease, which often include low muscle tone and muscle weakness.

Babies affected by the disease may have feeding difficulties or trouble breathing. Children may show signs of developmental delays, learning difficulties, hearing loss and epilepsy.

Muscle weakness may also affect the facial muscles and lead to facial paralysis, droopy eyelids and difficulty moving the eyes.

Most common in patients with late-onset disease, which occurs when symptoms appear after age 12, weakness in the shoulder muscles can cause the shoulder blade to stick out, also known as scapular winging.

Blood tests

A doctor may also suggest a blood test to check the levels of creatine kinase (CK).

CK is an enzyme found in the skeletal muscles, heart muscle and brain. If muscles are damaged, it can leak into the bloodstream and be detected by a blood test.

The levels of CK are elevated in patients with TK2d. However, CK levels are not specific to this disease, and other conditions can also cause CK levels to be elevated.

Electromyography

An electromyography allows doctors to see how TK2d has affected the muscles.

In this test, doctors record the muscle’s responses to an electric stimulation. One or more electrodes are inserted into the muscle to record its electrical activity, which is displayed on a monitor in the form of waves. 

An electromyography can also pick up the myopathic changes that occur in the muscles of patients with TK2d.

Muscle biopsy

A muscle biopsy can further help identify changes that occur in the muscle tissue due to TK2d. It involves the removal of a small portion of muscle tissue, which is then stained and viewed under a microscope.

Muscle biopsies from a patient with TK2d typically show abnormalities in the mitochondria and contain abundant ragged-red fibers.

Brain imaging tests

Brain imaging tests, like a computed tomography (CT) scan or a magnetic resonance imaging (MRI), may help visualize the changes that occur in the brain due to TK2d.

Genetic testing

Genetic testing for variants of the TK2 gene can confirm a diagnosis of TK2d. 

Here, a small blood sample is taken to isolate DNA from it. 

There are over 30 mutations in the TK2 gene that are known to be associated with TK2d. The identification of any one of these genes can confirm a diagnosis of the disease.