TK2d Basics

Thymidine Kinase 2 deficiency (TK2d) is an ultra-rare genetic disease that mainly affects the muscles. 

A disease is considered ultra-rare when it affects fewer than one in 50,000 people. It is estimated that TK2d affects around 600 to 2,700 people in the U.S.

What causes TK2d?

TK2d is caused by a mutation in the TK2 gene, which contains the information necessary to make the TK2 protein. The role of this protein is to help make certain building blocks that are necessary to maintain the DNA of mitochondria, which are known as the “power plants” of the cell.

When the TK2 protein does not function properly because of a mutation in the gene that codes for it, the amount of DNA inside each mitochondrion depletes over time, leading to the mitochondria not being able to produce the energy needed by the cells.

TK2d is inherited in a recessive manner. This means that the disease develops only when a recessive gene is inherited from both parents, meaning both the mother and father carried the gene. Having only one copy of the recessive gene does not lead to the disease.

Who is affected by TK2d?

TK2d can affect both men and women and does not seem to affect one ethnic group more than another.

What are the symptoms of TK2d?

There are three different types of TK2d: early-onset, childhood-onset and late-onset TK2d. The symptoms vary by the type of disease, but general symptoms of TK2d in all its forms include muscle weakness in the arms, the legs and the muscles used for swallowing and breathing.

Patients with early-onset disease, which usually begins before the age of 1, may also have symptoms like epilepsy, heart and kidney complications and multiple bone fractures. This type of disease usually progresses rapidly, and patients have a general prognosis of 1 to 2 years.

Symptoms of childhood- and late-onset TK2d may include difficulty or inability to move the eyes, droopy eyelids, breathing difficulties and hearing loss. These symptoms usually appear between the ages of one and 12 in childhood-onset TK2d and after age 12 in patients with late-onset disease.

How do doctors diagnose TK2d?

Doctors can diagnose TK2d based on a patient’s symptoms, medical history and clinical examination.

They may also conduct laboratory tests, checking, for example, for the levels of creatine kinase, which is elevated in case of TK2d and electromyography tests.

They may also recommend a muscle biopsy for analysis and conduct imaging tests such as computed tomography (CT) or magnetic resonance imaging (MRI).

Genetic tests that show changes in the TK2 gene can confirm the diagnosis of TK2d.

How is TK2d treated?

There is currently no cure for TK2d, but in November 2025, the U.S. Food and Drug Administration approved Kygevvi (doxecitine and doxribtimine) powder to treat thymidine kinase 2 deficiency (TK2d) in adults and pediatric patients who start to show symptoms when they are 12 years old or younger.

It works by supplying DNA building blocks to the mitochondria in muscle cells to restore the number of mitochondrial DNA (mtDNA) copies and improve muscle function.

Other treatment approaches focus on alleviating the symptoms of the disease and improving patients’ quality of life. They may include chest physiotherapy, physical and occupational therapy, ventilatory support, cochlear implants for hearing loss, mobility aids like a wheelchair and anti-seizure medications.