TK2-related mitochondrial DNA depletion syndrome, myopathic form (TK2-MDS) is an autosomal recessive condition. To date, approximately 45 individuals with TK2-MDS have been reported. The symptoms of TK2-MDS typically begin in early childhood, and range from severe to mild. The most typical presentation is progressive muscle disease characterized by generalized hypotonia, proximal muscle weakness, loss of previously acquired motor skills, poor feeding, and respiratory difficulties. TK2-MDS usually affects the muscles. However, other presentations may occur including hepatomegaly, seizures, and sensorineural hearing loss. The most common cause of death in people with TK2-MDS is respiratory failure, often occurring within a few years after diagnosis.

Diagnosis is based on elevated serum creatine phosphokinase (CK) concentration, and characteristic histopathologic findings in skeletal muscle as well as increased succinate dehydrogenase (SDH) activity and low-to-absent cytochrome c oxidase (COX) activity. There is no treatment for TK2-MDS.

Mutations in the TK2 gene are the cause of TK2-related mitochondrial DNA depletion syndrome, myopathic form. These mutations reduce the production or activity of thymidine kinase 2, leading to mtDNA depletion. Patients with TK2-MDS have very low amounts of mtDNA in the muscle tissues, ranging from 5% to 30% percent of normal values.