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.
Three unrelated Arab patients (two females and a male) with Mitochondrial DNA Depletion Syndrome were described by Saada et al. (2001). Two of the patients had consanguineous parents and had a family history of several siblings having died from a degenerative muscle disease. The patients seemed normal at birth and had an uneventful early development, apart from a mild to moderate muscle hypotonia. By 2-years of age, the patients had become considerably weaker and began to lose previously acquired motor skills, although cognitive functions were normal. Biochemical tests showed elevated creatine kinase and slightly elevated plasma lactate levels. There was no clinical or biochemical involvement of any other organs. The enzymatic activity of mitochondrial respiratory chain complexes I, III, IV, and V was significantly reduced, while that of complex II was normal. One of the female patients died at 19-months of age, while the other two patients required mechanical ventilated at 3-years.
Al-Shamsi et al. (2014) undertook a study to calculate the birth prevalence of IEMs among Emiratis in the UAE by taking into consideration all neonates born with an inherited metabolic condition at Tawam Hospital between 1995 and 2012. A total of 37 distinct IEMs were found in Emirati neonates in this study, providing an estimated IEM birth prevalence of 75.24 per 100,000 live births. Mitochondrial DNA Depletion Syndromes were found to have a birth prevalence of between 2.2 and 4.9 per 100,000. A single mutation in the TK2 gene was identified in patient(s) affected by the myopathic form of the condition.