SEVERE TK2 ENZYME ACTIVITY DEFICIENCY IN PATIENTS WITH MILD FORMS OF MYOPATHY

被引:20
作者
Camara, Yolanda [1 ,4 ]
Carreno-Gago, Lidia [1 ,4 ]
Martin, Miguel A. [4 ,5 ]
Melia, Maria J. [1 ,4 ]
Blazquez, Alberto [4 ,5 ]
Delmiro, Aitor [4 ,5 ]
Garrabou, Gloria [4 ,7 ]
Moren, Constanza [4 ,7 ]
Diaz-Manera, Jorge [2 ,3 ,4 ]
Gallardo, Eduard [2 ,3 ,4 ]
Bornstein, Belen [4 ,8 ]
Lopez-Gallardo, Ester [4 ,9 ]
Hernandez-Lain, Aurelio [6 ]
San Millan, Beatriz [10 ]
Cancho, Esther [11 ]
Samuel Rodriguez-Vico, Jaime [12 ]
Marti, Ramon [1 ,4 ]
Garcia-Arumi, Elena [1 ,4 ]
机构
[1] Univ Autonoma Barcelona, Vall dHebron Inst Recerca, Res Grp Neuromuscular & Mitochondrial Disorders, E-08193 Barcelona, Spain
[2] Univ Autonoma Barcelona, Serv Neurol, Lab Neurol Expt, Hosp Santa Creu & St Pau, E-08193 Barcelona, Spain
[3] Univ Autonoma Barcelona, Inst Recerca HSCSP, E-08193 Barcelona, Spain
[4] Inst Salud Carlos III, Biomed Network Res Ctr Rare Dis CIBERER, Madrid, Spain
[5] Inst Invest Hosp 12 Octubre I 12, Lab Enfermedades Mitocondriales, Madrid, Spain
[6] Inst Invest Hosp 12 Octubre I 12, Secc Neuropatol, Madrid, Spain
[7] Univ Barcelona, Fac Med, Hosp Clin Barcelona, Muscle Res & Mitochondrial Funct Lab,Cellex IDIBA, Barcelona 7, Spain
[8] Hosp Univ Puerta Hierro, Biochem Unit, Madrid, Spain
[9] Univ Zaragoza, Dept Bioquim Biol Mol & Celular, Zaragoza, Spain
[10] Complejo Hosp Univ Vigo, Serv Anat Patol, Vigo, Spain
[11] Hosp Don Benito Villanueva, Serv Neurol, Badajoz, Spain
[12] Hosp Univ Burgos, Serv Neurol, Burgos, Spain
关键词
MITOCHONDRIAL-DNA DEPLETION; MUTATIONS; DELETIONS; GENE;
D O I
10.1212/WNL.0000000000001644
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Thymidine kinase 2 (TK2) is a mitochondrial enzyme participating in the salvage of deoxyribonucleotides needed for mitochondrial DNA (mtDNA) replication. TK2 catalyzes the first and rate-limiting step of the deoxypyrimidine salvage pathway. Mutations in TK2 were typically associated with a severe myopathic form of mtDNA depletion syndrome (MDS) characterized by a dramatic decrease in mtDNA copy number in muscle that manifests during infancy and leads to the early death of most patients.(1) Recently, several patients have been diagnosed with a late-onset or slow-progressing form of the disease manifesting as a milder myopathy with mtDNA multiple deletions.(2-5) Here we describe 7 adult cases presenting with a mild myopathy compatible with a relatively normal life for decades and associated with multiple mtDNA deletions and no marked depletion in skeletal muscle. TK2 activity was drastically reduced in cultured fibroblasts of 2 of these patients, suggesting that redundant or complementary biochemical mechanisms could bypass the defect in some individuals, in contrast with severely affected infantile patients.
引用
收藏
页码:2286 / 2288
页数:3
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