Clinical spectrum of mitochondrial DNA depletion due to mutations in the thymidine kinase 2 gene

Maryam Oskoui, Guido Davidzon, Juan Pascual, Ricardo Erazo, Juliana Gurgel-Giannetti, Sindu Krishna, Eduardo Bonilla, Darryl C. De Vivo, Sara Shanske, Salvatore DiMauro

Research output: Contribution to journalArticle

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Abstract

Background: Mitochondrial DNA depletion syndrome is an autosomal recessive disorder characterized by decreased mitochondrial DNA copy numbers in affected tissues. It has been linked to 4 genes involved in deoxyribonucleotide triphosphate metabolism: thymidine kinase 2 (TK2), deoxyguanosine kinase (DGUOK), polymerase gamma (POLG), and SUCLA2, the gene encoding the β-subunit of the adenosine diphosphate-forming succinyl coenzyme A synthetase ligase. Objective: To highlight the variability in the clinical spectrum of TK2-related mitochondrial DNA depletion syndrome. Design: Review of patients and the literature. Setting: Tertiary care university. Patients: Four patients with mitochondrial DNA depletion syndrome and mutations in the TK2 gene. Main Outcome Measures: Definition of clinical variability. Results: Patient 1 had evidence of lower motoneuron disease and was initially diagnosed as having spinal muscular atrophy type 3. Patient 2, who is alive and ambulatory at age 9 years, presented at age 2 years with a slowly progressive mitochondrial myopathy. Patient 3 had a more severe myopathy, with onset in infancy and death at age 6 years of respiratory failure. Patient 4 had a rapidly progressive congenital myopathy with rigid spine syndrome and he died at age 19 months. Conclusion: The clinical spectrum of TK2 mutations is not limited to severe infantile myopathy with motor regression and early death but includes spinal muscular atrophy type 3-like presentation, rigid spine syndrome, and subacute myopathy without motor regression and with longer survival.

Original languageEnglish (US)
Pages (from-to)1122-1126
Number of pages5
JournalArchives of Neurology
Volume63
Issue number8
DOIs
StatePublished - Aug 2006

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Mitochondrial DNA
Mutation
Genes
Muscular Diseases
Spinal Muscular Atrophies of Childhood
deoxyguanosine kinase
Succinate-CoA Ligases
Mitochondrial Myopathies
Myotonia Congenita
Coenzyme A Ligases
Deoxyribonucleotides
Motor Neurons
Tertiary Healthcare
thymidine kinase 2
Gene
Respiratory Insufficiency
Adenosine Diphosphate
Outcome Assessment (Health Care)
Syndrome
Survival

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Oskoui, M., Davidzon, G., Pascual, J., Erazo, R., Gurgel-Giannetti, J., Krishna, S., ... DiMauro, S. (2006). Clinical spectrum of mitochondrial DNA depletion due to mutations in the thymidine kinase 2 gene. Archives of Neurology, 63(8), 1122-1126. https://doi.org/10.1001/archneur.63.8.1122

Clinical spectrum of mitochondrial DNA depletion due to mutations in the thymidine kinase 2 gene. / Oskoui, Maryam; Davidzon, Guido; Pascual, Juan; Erazo, Ricardo; Gurgel-Giannetti, Juliana; Krishna, Sindu; Bonilla, Eduardo; De Vivo, Darryl C.; Shanske, Sara; DiMauro, Salvatore.

In: Archives of Neurology, Vol. 63, No. 8, 08.2006, p. 1122-1126.

Research output: Contribution to journalArticle

Oskoui, M, Davidzon, G, Pascual, J, Erazo, R, Gurgel-Giannetti, J, Krishna, S, Bonilla, E, De Vivo, DC, Shanske, S & DiMauro, S 2006, 'Clinical spectrum of mitochondrial DNA depletion due to mutations in the thymidine kinase 2 gene', Archives of Neurology, vol. 63, no. 8, pp. 1122-1126. https://doi.org/10.1001/archneur.63.8.1122
Oskoui, Maryam ; Davidzon, Guido ; Pascual, Juan ; Erazo, Ricardo ; Gurgel-Giannetti, Juliana ; Krishna, Sindu ; Bonilla, Eduardo ; De Vivo, Darryl C. ; Shanske, Sara ; DiMauro, Salvatore. / Clinical spectrum of mitochondrial DNA depletion due to mutations in the thymidine kinase 2 gene. In: Archives of Neurology. 2006 ; Vol. 63, No. 8. pp. 1122-1126.
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