title: Clinical spectrum of mitochondrial DNA depletion due to mutations in the thymidine kinase 2 gene.
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 beta-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.
  
  
  METHODS
  Review of patients and the literature.
  
  
  METHODS
  Tertiary care university.
  
  
  METHODS
  Four patients with mitochondrial DNA depletion syndrome and mutations in the TK2 gene.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Neurology, Columbia University Medical Center, 630 West 168th Street, New York, NY 10032, USA.
authors.forename: Maryam
authors.initials: M
authors.lastname: Oskoui
authors.forename: Guido
authors.initials: G
authors.lastname: Davidzon
authors.forename: Juan
authors.initials: J
authors.lastname: Pascual
authors.forename: Ricardo
authors.initials: R
authors.lastname: Erazo
authors.forename: Juliana
authors.initials: J
authors.lastname: Gurgel-Giannetti
authors.forename: Sindu
authors.initials: S
authors.lastname: Krishna
authors.forename: Eduardo
authors.initials: E
authors.lastname: Bonilla
authors.forename: Darryl C
authors.initials: DC
authors.lastname: De Vivo
authors.forename: Sara
authors.initials: S
authors.lastname: Shanske
authors.forename: Salvatore
authors.initials: S
authors.lastname: DiMauro
mesh_terms: D000293:Adolescent; D002648:Child; D004272:DNA, Mitochondrial / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D028361:Mitochondrial Diseases / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D013937:Thymidine Kinase / Q000235:genetics* / Q000378:metabolism
chemical_list: D004272:DNA, Mitochondrial; C105339:thymidine kinase 2; D013937:Thymidine Kinase