Abstract：
OBJECTIVE: Riboflavin transporter deficiency (RTD) is a progressive inherited neuropathy of childhood onset, characterised clinically by pontobulbar palsy, sensory ataxia, sensorineural deafness, muscle weakness, optic atrophy and respiratory failure. A robust and responsive functional outcome measure is essential for future clinical trials of disease-modifying therapies including genetic therapies. The Charcot-Marie-Tooth disease Pediatric Scale (CMTPedS) is a well-validated outcome measure for CMT and related neuropathies, and might have utility for measuring disease progression in individuals with RTD. However, the CMTPedS requires modifications to account for phenotypic differences between children with CMT and RTD. The aim of this study was to develop a functional outcome measure based on the CMTPedS for specific use in individuals with RTD.
METHODS: The CMTPedS data collected over the last 10 years in individuals with RTD attending the Peripheral Neuropathy Management Clinic at the Children\'s Hospital at Westmead (Sydney, Australia) were reviewed to evaluate each item within the CMTPedS. A literature review of articles published until September 2021 for functional outcome measures generated an item pool for pilot testing. The results of this pilot testing, alongside analysis of existing CMTPedS item scores in the RTD cohort, informed the modification of the CMTPedS.
RESULTS: CMTPedS data were reviewed for eight individuals over the past 10 years. Two items were identified as requiring modification or removal and additional items of proximal strength and function needed to be considered. Six studies were identified in the literature review, and five items were selected for pilot testing. \'Shoulder internal rotation\' and the \'30-s sit to stand test\' were added as proximal measures of strength and function. The composite balance item comprising nine tasks in the CMTPedS showed a ceiling effect and was replaced with the single \'Feet apart on a line eyes open\' balance item. \'Pinprick sensation\' was removed due to a floor effect.
CONCLUSIONS: This study provides preliminary evidence that the Riboflavin Transporter Deficiency Pediatric Scale (RTDPedS) is a functional outcome measure covering strength, upper and lower limb function, balance and mobility for individuals with RTD to assess disease severity and progression in clinical trials and cohort studies.
METHODS: The CMTPedS data collected over the last 10 years in individuals with RTD attending the Peripheral Neuropathy Management Clinic at the Children\'s Hospital at Westmead (Sydney, Australia) were reviewed to evaluate each item within the CMTPedS. A literature review of articles published until September 2021 for functional outcome measures generated an item pool for pilot testing. The results of this pilot testing, alongside analysis of existing CMTPedS item scores in the RTD cohort, informed the modification of the CMTPedS.
RESULTS: CMTPedS data were reviewed for eight individuals over the past 10 years. Two items were identified as requiring modification or removal and additional items of proximal strength and function needed to be considered. Six studies were identified in the literature review, and five items were selected for pilot testing. \'Shoulder internal rotation\' and the \'30-s sit to stand test\' were added as proximal measures of strength and function. The composite balance item comprising nine tasks in the CMTPedS showed a ceiling effect and was replaced with the single \'Feet apart on a line eyes open\' balance item. \'Pinprick sensation\' was removed due to a floor effect.
CONCLUSIONS: This study provides preliminary evidence that the Riboflavin Transporter Deficiency Pediatric Scale (RTDPedS) is a functional outcome measure covering strength, upper and lower limb function, balance and mobility for individuals with RTD to assess disease severity and progression in clinical trials and cohort studies.
摘要：
目的：核黄素转运体缺乏症（RTD）是一种儿童期发病的进行性遗传性神经病变，临床特征为浮球麻痹，感觉共济失调,感觉神经性耳聋,肌肉无力,视神经萎缩和呼吸衰竭。稳健和响应的功能结果测量对于包括基因疗法在内的疾病修饰疗法的未来临床试验至关重要。Charcot-Marie-Tooth疾病儿科量表（CMTPedS）是CMT和相关神经病的经过充分验证的结果指标，并可能用于测量RTD患者的疾病进展。然而,CMTPedS需要修改以解释CMT和RTD患儿之间的表型差异.这项研究的目的是开发一种基于CMTPedS的功能结果度量，用于RTD患者的特定用途。
方法：在过去10年中，在Westmead儿童医院（悉尼，澳大利亚）进行了审查，以评估CMTPedS中的每个项目。直到2021年9月发表的关于功能结果测量的文章的文献综述产生了一个用于试点测试的项目池。这个试点测试的结果，除了分析RTD队列中现有的CMTPedS项目得分，通知了CMTPedS的修改。
结果：CMTPedS数据在过去10年中对8个人进行了回顾。确定了两个项目需要修改或移除，并且需要考虑近端强度和功能的其他项目。在文献综述中确定了六项研究，并选择了五个项目进行试点测试。增加了“肩部内旋”和“30秒站立测试”作为强度和功能的近端测量。CMTPedS中包含9个任务的复合平衡项目显示出天花板效果，并被替换为“双脚分开”平衡项目。由于地板效应，“针刺感”被删除。
结论：这项研究提供了初步证据，证明核黄素转运蛋白缺乏症儿科量表（RTDPedS）是一种功能结局指标，包括强度，上肢和下肢功能，在临床试验和队列研究中评估RTD患者疾病严重程度和进展的平衡和流动性。
方法：在过去10年中，在Westmead儿童医院（悉尼，澳大利亚）进行了审查，以评估CMTPedS中的每个项目。直到2021年9月发表的关于功能结果测量的文章的文献综述产生了一个用于试点测试的项目池。这个试点测试的结果，除了分析RTD队列中现有的CMTPedS项目得分，通知了CMTPedS的修改。
结果：CMTPedS数据在过去10年中对8个人进行了回顾。确定了两个项目需要修改或移除，并且需要考虑近端强度和功能的其他项目。在文献综述中确定了六项研究，并选择了五个项目进行试点测试。增加了“肩部内旋”和“30秒站立测试”作为强度和功能的近端测量。CMTPedS中包含9个任务的复合平衡项目显示出天花板效果，并被替换为“双脚分开”平衡项目。由于地板效应，“针刺感”被删除。
结论：这项研究提供了初步证据，证明核黄素转运蛋白缺乏症儿科量表（RTDPedS）是一种功能结局指标，包括强度，上肢和下肢功能，在临床试验和队列研究中评估RTD患者疾病严重程度和进展的平衡和流动性。
