Late-onset thymidine kinase 2 deficiency: a review of 18 cases
Por:
Dominguez-Gonzalez, C, Hernandez-Lain, A, Rivas, E, Hernandez-Voth, A, Catalan, JS, Fernandez-Torron, R, Fuiza-Luces, C, Garcia, JG, Moris, G, Olive, M, Miralles, F, Diaz-Manera, J, Caballero, C, Mendez-Ferrer, B, Marti, R, Arumi, EG, Badosa, MC, Esteban, J, Jimenez-Mallebrera, C, Encinar, AB, Arenas, J, Hirano, M, Martin, MA, Paradas, C
Publicada:
6 may 2019
Resumen:
BackgroundTK2 gene encodes for mitochondrial thymidine kinase, which phosphorylates the pyrimidine nucleosides thymidine and deoxycytidine. Recessive mutations in the TK2 gene are responsible for the myopathic form' of the mitochondrial depletion/multiple deletions syndrome, with a wide spectrum of severity.MethodsWe describe 18 patients with mitochondrial myopathy due to mutations in the TK2 gene with absence of clinical symptoms until the age of 12.ResultsThe mean age of onset was 31years. The first symptom was muscle limb weakness in 10/18, eyelid ptosis in 6/18, and respiratory insufficiency in 2/18. All patients developed variable muscle weakness during the evolution of the disease. Half of patients presented difficulty in swallowing. All patients showed evidence of respiratory muscle weakness, with need for non-invasive Mechanical Ventilation in 12/18. Four patients had deceased, all of them due to respiratory insufficiency. We identified common radiological features in muscle magnetic resonance, where the most severely affected muscles were the gluteus maximus, semitendinosus and sartorius. On muscle biopsies typical signs of mitochondrial dysfunction were associated with dystrophic changes. All mutations identified were previously reported, being the most frequent the in-frame deletion p.Lys202del. All cases showed multiple mtDNA deletions but mtDNA depletion was present only in two patients.ConclusionsThe late-onset is the less frequent form of presentation of the TK2 deficiency and its natural history is not well known. Patients with late onset TK2 deficiency have a consistent and recognizable clinical phenotype and a poor prognosis, due to the high risk of early and progressive respiratory insufficiency.
Filiaciones:
Dominguez-Gonzalez, C:
12 Octubre Hosp, Neurol Dept, Neuromuscular Disorders Unit, Madrid, Spain
12 Octubre Hosp, Res Inst I 12, Madrid, Spain
Inst Salud Carlos III, Biomed Network Res Ctr Rare Dis CIBERER, Madrid, Spain
Hernandez-Lain, A:
12 Octubre Hosp, Pathol Dept, Neuromuscular Disorders Unit, Neuropathol, Madrid, Spain
Rivas, E:
Univ Seville, Hosp Univ Virgen del Rocio, Pathol Anat Dept,CSIC, Neuromuscular Disorders Unit,Inst Biomed Sevilla, Seville, Spain
Hernandez-Voth, A:
12 Octubre Hosp, Neumol Dept, Neuromuscular Disorders Unit, Madrid, Spain
Catalan, JS:
12 Octubre Hosp, Neumol Dept, Neuromuscular Disorders Unit, Madrid, Spain
Fernandez-Torron, R:
Hosp Donostia, Neuromuscular Disorders Unit, Neurol Dept, San Sebastian, Spain
Fuiza-Luces, C:
12 Octubre Hosp, Res Inst I 12, Madrid, Spain
Inst Salud Carlos III, Biomed Network Res Ctr Rare Dis CIBERER, Madrid, Spain
Hosp 12 Octubre I 12, Res Inst, Mitochondrial & Neuromuscular Dis Lab, Madrid, Spain
Garcia, JG:
Hosp Albacete, Neurol Dept, Albacete, Spain
Moris, G:
Hosp Cent Asturias, Neurol Dept, Neuromuscular Disorders Unit, Oviedo, Spain
Olive, M:
Hosp Bellvitge Princeps Espanya, IDIBELL, Neuromuscular Disorders Unit, Pathol Anat Dept, Barcelona, Spain
Miralles, F:
Hosp Univ Son Espases, Neurol Dept, Neuromuscular Disorders Unit, Palma De Mallorca, Spain
Diaz-Manera, J:
Inst Salud Carlos III, Biomed Network Res Ctr Rare Dis CIBERER, Madrid, Spain
Hosp Santa Creu & Sant Pau, Neurol Dept, Neuromuscular Disorders Unit, Barcelona, Spain
Caballero, C:
Univ Seville, Inst Biomed Sevilla, Resp Dept, Hosp Univ Virgen del Rocio,CSIC,CIBERES, Seville, Spain
Mendez-Ferrer, B:
Hosp Virgen del Rocio, Rehabil Dept, Seville, Spain
Marti, R:
Inst Salud Carlos III, Biomed Network Res Ctr Rare Dis CIBERER, Madrid, Spain
Hosp St Joan de Deu, Inst Recerca St Joan de Deu, Neurol Dept, Neuromuscular Unit, Barcelona, Spain
Arumi, EG:
Inst Salud Carlos III, Biomed Network Res Ctr Rare Dis CIBERER, Madrid, Spain
Univ Autonoma Barcelona, ValldHebron Res Inst, Res Grp Neuromuscular & Mitochondrial Dis, Barcelona, Spain
Badosa, MC:
Hosp St Joan de Deu, Inst Recerca St Joan de Deu, Neurol Dept, Neuromuscular Unit, Barcelona, Spain
Esteban, J:
12 Octubre Hosp, Neurol Dept, Neuromuscular Disorders Unit, Madrid, Spain
12 Octubre Hosp, Res Inst I 12, Madrid, Spain
Inst Salud Carlos III, Biomed Network Res Ctr Rare Dis CIBERER, Madrid, Spain
Jimenez-Mallebrera, C:
Inst Salud Carlos III, Biomed Network Res Ctr Rare Dis CIBERER, Madrid, Spain
Hosp St Joan de Deu, Inst Recerca St Joan de Deu, Neurol Dept, Neuromuscular Unit, Barcelona, Spain
Encinar, AB:
12 Octubre Hosp, Res Inst I 12, Madrid, Spain
Inst Salud Carlos III, Biomed Network Res Ctr Rare Dis CIBERER, Madrid, Spain
Hosp 12 Octubre I 12, Res Inst, Mitochondrial & Neuromuscular Dis Lab, Madrid, Spain
Arenas, J:
12 Octubre Hosp, Res Inst I 12, Madrid, Spain
Inst Salud Carlos III, Biomed Network Res Ctr Rare Dis CIBERER, Madrid, Spain
Hosp 12 Octubre I 12, Res Inst, Mitochondrial & Neuromuscular Dis Lab, Madrid, Spain
Hirano, M:
Columbia Univ, Med Ctr, H Houston Merritt Ctr, Dept Neurol, New York, NY USA
Martin, MA:
12 Octubre Hosp, Res Inst I 12, Madrid, Spain
Inst Salud Carlos III, Biomed Network Res Ctr Rare Dis CIBERER, Madrid, Spain
Hosp 12 Octubre I 12, Res Inst, Mitochondrial & Neuromuscular Dis Lab, Madrid, Spain
Paradas, C:
Univ Seville, CSIC, Hosp Univ Virgen del Rocio, Neurol Dept,Neuromuscular Disorders Unit,Inst Bio, Avd Manuel Siurot S-N, Seville 41013, Spain
Biomed Network Res Ctr Neurodegenerat Dis CIBERNE, Madrid, Spain
Gold, Green Published
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