Abstract：
OBJECTIVE: Thymidine kinase 2 deficiency (TK2d) is a rare autosomal recessive mitochondrial disorder. It manifests as a continuous clinical spectrum, from fatal infantile mitochondrial DNA depletion syndromes to adult-onset mitochondrial myopathies characterized by ophthalmoplegia-plus phenotypes with early respiratory involvement. Treatment with pyrimidine nucleosides has recently shown striking effects on survival and motor outcomes in the more severe infantile-onset clinical forms. We present the response to treatment in a patient with adult-onset TK2d.
METHODS: An adult with ptosis, ophthalmoplegia, facial, neck, and proximal muscle weakness, non-invasive nocturnal mechanical ventilation, and dysphagia due to biallelic pathogenic variants in TK2 received treatment with 260 mg/kg/day of deoxycytidine (dC) and deoxythymidine (dT) under a Compassionate Use Program. Prospective motor and respiratory assessments are presented.
RESULTS: After 27 months of follow-up, the North Star Ambulatory Assessment improved by 11 points, he walked 195 m more in the 6 Minute-Walking-Test, ran 10 s faster in the 100-meter time velocity test, and the Forced Vital Capacity stabilized. Growth Differentiation Factor-15 (GDF15) levels, a biomarker of respiratory chain dysfunction, normalized. The only reported side effect was dose-dependent diarrhea.
CONCLUSIONS: Treatment with dC and dT can significantly improve motor performance and stabilize respiratory function safely in patients with adult-onset TK2d.
METHODS: An adult with ptosis, ophthalmoplegia, facial, neck, and proximal muscle weakness, non-invasive nocturnal mechanical ventilation, and dysphagia due to biallelic pathogenic variants in TK2 received treatment with 260 mg/kg/day of deoxycytidine (dC) and deoxythymidine (dT) under a Compassionate Use Program. Prospective motor and respiratory assessments are presented.
RESULTS: After 27 months of follow-up, the North Star Ambulatory Assessment improved by 11 points, he walked 195 m more in the 6 Minute-Walking-Test, ran 10 s faster in the 100-meter time velocity test, and the Forced Vital Capacity stabilized. Growth Differentiation Factor-15 (GDF15) levels, a biomarker of respiratory chain dysfunction, normalized. The only reported side effect was dose-dependent diarrhea.
CONCLUSIONS: Treatment with dC and dT can significantly improve motor performance and stabilize respiratory function safely in patients with adult-onset TK2d.
摘要：
目的：胸苷激酶2缺乏症（TK2d）是一种罕见的常染色体隐性遗传线粒体疾病。它表现为连续的临床谱，从致命的婴儿线粒体DNA耗竭综合征到以眼肌麻痹+早期呼吸道受累表型为特征的成人发病线粒体肌病。最近，嘧啶核苷治疗对更严重的婴儿发作临床形式的生存和运动结局显示出惊人的影响。我们介绍了成人发作的TK2d患者对治疗的反应。
方法：成人上睑下垂，眼肌麻痹,面部,脖子,和近端肌肉无力，无创夜间机械通气，和吞咽困难由于双等位基因致病性变异TK2接受了260mg/kg/天的脱氧胞苷（dC）和脱氧胸苷（dT）的治疗根据一个体恤使用计划。提出了前瞻性的运动和呼吸评估。
结果：经过27个月的随访，北极星门诊评估提高了11分，他在6分钟步行测试中又走了195米，在100米时间速度测试中跑得更快10秒，强迫生命能力稳定了.生长分化因子-15（GDF15）水平，呼吸链功能障碍的生物标志物，归一化。唯一报道的副作用是剂量依赖性腹泻。
结论：使用dC和dT治疗可以显著改善成年TK2d患者的运动能力并安全稳定呼吸功能。
方法：成人上睑下垂，眼肌麻痹,面部,脖子,和近端肌肉无力，无创夜间机械通气，和吞咽困难由于双等位基因致病性变异TK2接受了260mg/kg/天的脱氧胞苷（dC）和脱氧胸苷（dT）的治疗根据一个体恤使用计划。提出了前瞻性的运动和呼吸评估。
结果：经过27个月的随访，北极星门诊评估提高了11分，他在6分钟步行测试中又走了195米，在100米时间速度测试中跑得更快10秒，强迫生命能力稳定了.生长分化因子-15（GDF15）水平，呼吸链功能障碍的生物标志物，归一化。唯一报道的副作用是剂量依赖性腹泻。
结论：使用dC和dT治疗可以显著改善成年TK2d患者的运动能力并安全稳定呼吸功能。
