Deoxynucleoside therapy for respiratory involvement in adult patients with thymidine kinase 2-deficient myopathy

被引:14
作者
Hernandez-Voth, Ana [1 ,2 ]
Sayas Catalan, Javier [1 ,2 ,3 ]
Corral Blanco, Marta [1 ,2 ]
Castano Mendez, Alba [1 ]
Martin, Miguel Angel [3 ,4 ,5 ]
de Fuenmayor Fernandez de la Hoz, Carlos [2 ]
Villena Garrido, Victoria [3 ,6 ,7 ,8 ]
Dominguez-Gonzalez, Cristina [2 ,3 ,9 ]
机构
[1] Hosp Univ 12 Octubre, Unidad Ventilac Mecan, Serv Neumol, Madrid, Spain
[2] Hosp Univ 12 Octubre, Unidad Enfermedades Neuromusculares, Serv Neurol, Madrid, Spain
[3] Hosp Univ 12 Octubre, Inst Invest imas12, Madrid, Spain
[4] Hosp Univ 12 Octubre, Lab Enfermedades Mitocondri, Dept Bioquim, Madrid, Spain
[5] Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Raras, Madrid, Spain
[6] Univ Complutense Madrid, Fac Med, Dept Med, Madrid, Spain
[7] Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Resp CIBERES, Madrid, Spain
[8] Hosp Univ 12 Octubre, Serv Neumol, Madrid, Spain
[9] Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Raras CIBERER, Madrid, Spain
关键词
non invasive ventilation; respiratory muscles; rare lung diseases; FORCE;
D O I
10.1136/bmjresp-2020-000774
中图分类号
R56 [呼吸系及胸部疾病];
学科分类号
摘要
Background Recessive mutations in the thymidine kinase 2 (TK2) gene cause a rare mitochondrial myopathy, frequently with severe respiratory involvement. Deoxynucleoside therapy is currently under investigation. Research question What is the impact of nucleosides in respiratory function in patients with TK2-deficient myopathy? Study design and methods Retrospective observational study of patients treated with deoxycytidine and deoxythymidine. Evaluations were performed every 3 to 4 months after treatment during approximately 30 months. Forced vital capacity (FVC), maximuminspiratory and expiratory pressures (MIP/MEP), sniff nasal inspiratory pressure (SNIP), cough peak flow (CPF), arterial blood gas and nocturnal pulse oximeter (SpO2) were collected. Results We studied six patients, five of which were women, with a median age at onset of symptoms was 35.8 (range 5 to 60) years old. Patients presented a restrictive ventilatory pattern (median FVC of 50 (26 to 71)%) and severe neuromuscular respiratory weakness (MIP 38 (12 to 47)% and SNIP 14 (8 to 19) cmH2O). Four patients required ventilatory support before starting the treatment. FVC improved by 6%, proportion of sleep time with SpO2 <90% diminished from 14% to 0%, CPF increased by 23%, MEP increased by 73%, production and management of bronchial secretions improved and respiratory infections diminished. Interpretation Early detection of respiratory involvement requires an active search, even in asymptomatic patients. The nucleosides therapy may improve respiratory function, and stabilise the loss of respiratory capacity.
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页数:6
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