Send to

Choose Destination

TK2-Related Mitochondrial DNA Maintenance Defect, Myopathic Form.


GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2019.
2012 Dec 6 [updated 2018 Jul 26].

Author information

Baylor College of Medicine, Houston, Texas
Associate Professor, Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates



TK2-related mitochondrial DNA (mtDNA) maintenance defect is a phenotypic continuum that ranges from severe to mild. To date, approximately 107 individuals with a molecularly confirmed diagnosis have been reported. Three main subtypes of presentation have been described: Infantile-onset myopathy with neurologic involvement and rapid progression to early death. Affected individuals experience progressive muscle weakness leading to respiratory failure. Some individuals develop dysarthria, dysphagia, and/or hearing loss. Cognitive function is typically spared. Juvenile/childhood onset with generalized proximal weakness and survival to at least 13 years. Late-/adult-onset myopathy with facial and limb weakness and mtDNA deletions. Some affected individuals develop respiratory insufficiency, chronic progressive external ophthalmoplegia, dysphagia, and dysarthria.


The diagnosis of TK2-related mtDNA maintenance defect is established in a proband with infantile onset of disease with severely reduced (typically <20% of age- and tissue-matched healthy controls) mtDNA content in skeletal muscle. The diagnosis of TK2-related mtDNA maintenance defect is established in a proband older than age two years with reduced mtDNA content or multiple mtDNA deletions, ragged red fibers and/or COX-deficient fibers in skeletal muscle. The diagnosis is confirmed by the identification of biallelic pathogenic variants in TK2 by molecular genetic testing.


Treatment of manifestations: Management should involve a multidisciplinary team. Feeding difficulties should be managed aggressively, including use of a nasogastric tube or gastrostomy tube when the risk for aspiration is high. Physical therapy can help maintain muscle function; a physical medicine and rehabilitation (PM&R) specialist can help those who have difficulty walking. A pulmonologist can oversee chest physiotherapy to improve pulmonary function, reduce the risk of pulmonary infection, and manage respiratory insufficiency, if present. Hearing loss and seizures are managed in a standard manner. Prevention of secondary complications: Chest physiotherapy can help reduce the risk of pulmonary infection; physical therapy can help prevent joint contractures. Surveillance: No clinical guidelines are available. Treating physicians should consider: routine evaluation of growth and weight, pulmonary function tests with consideration of blood gases, neurodevelopmental assessments at each visit, and at least annual audiology evaluations in those with infantile-onset disease.


TK2-related mtDNA maintenance defect is inherited in an autosomal recessive manner. Each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk family members and prenatal testing for a pregnancy at increased risk are possible if the pathogenic variants in the family have been identified.

Copyright © 1993-2019, University of Washington, Seattle. GeneReviews is a registered trademark of the University of Washington, Seattle. All rights reserved.

Supplemental Content

Support Center