晚发型甲基丙二酸血症临床特征与综合康复治疗

关键词：晚发型甲基丙二酸血症  临床特征  MMACHC基因  康复

Keywords:late-onset methylmalonic acidemia  clinical characteristics  MMACHC gene  rehabilitation

摘要：

      摘要 目的：探讨晚发型甲基丙二酸血症（MMA）患者的临床特征及综合康复治疗的有效性。 方法：回顾性分析8例晚发型MMA患者的临床资料，包括就诊时的主要症状、体征、辅助检查、综合康复治疗。综合康复治疗包括药物及康复治疗，药物治疗包括：甲钴胺、甜菜碱、左卡尼汀，康复治疗主要是进行下肢肌力、平衡、步态训练。收集6例综合康复治疗患者治疗前后的徒手肌力、Holden步行功能分级、SF-36生命质量评分，采用Wilcoxon秩和检验方法进行治疗前后分析。 结果：8例中1例患者无症状，7例患者初始症状有反应迟钝、记忆力减退、精神淡漠等精神异常，行走不稳等运动障碍，关节疼痛、贫血、血栓等多系统损害。6例患者头颅MRI最突出表现为脑萎缩，1例患者头颅MRI表现为小脑异常信号。MMACHC基因最常见的两个变异为c.482G>A、c.394C>T。治疗12周后，患者精神异常症状消失，下肢肌力、Holden步行功能分级、SF-36评分较治疗前提高，差异均有显著性意义（P<0.05）。 结论：晚发型MMA患者临床异质性高，对于出现行走不稳、精神异常等多系统损害，应考虑该代谢病的可能性。综合康复治疗可明显改善晚发型MMA患者精神行为症状、肌力、步行功能及健康相关生命质量。

Abstract:

      Abstract Objective： To investigate the clinical characteristics and the effectiveness of comprehensive rehabilitation therapy in patients with late-onset methylmalonic acidemia （MMA）. Method： A retrospective analysis was conducted on clinical data of 8 patients with late-onset MMA， including the main symptoms， physical signs， auxiliary examinations， and comprehensive rehabilitation therapy. Comprehensive rehabilitation therapy consisted of medication and rehabilitation interventions. Medication included， methylcobalamin， betaine， and L-carnitine， while rehabilitation interventions focused on lower limb muscle strength training， balance training， and gait training. Manual muscle testing， Holden walking function classification， and SF-36 quality of life scores were collected from 6 patients before and after comprehensive rehabilitation therapy， and the Wilcoxon signed-rank test was used for pre- and post-treatment analysis. Result： Among the 8 patients， 1 was asymptomatic， while the remaining 7 exhibited initial symptoms such as neuropsychiatric abnormality including dull reaction， memory loss， and mental apathy， as well as motor impairments including unstable gait. Multiple systemic impairments such as joint pain， anemia， and thrombosis were also observed. The most prominent finding on cranial MRI in 6 patients was cerebral atrophy， while 1 patient showed abnormal signal in the cerebellum on cranial MRI. The two most common mutations in the MMACHC gene were c.482G>A and c.394C>T. After 12 weeks of treatment， the patients exhibited disappearance of psychiatric symptoms， improvement in lower limb muscle strength， Holden walking function classification， and SF-36 scores， with statistically significant differences （P<0.05）. Conclusion： Late-onset MMA demonstrates high clinical heterogeneity. For patients presenting with motor impairments and psychiatric abnormalities， the possibility of this metabolic disorder should be considered. Comprehensive rehabilitation therapy can significantly ameliorate psychiatric and behavior symptoms， muscle strength， walking function， and health-related quality of life in late-onset MMA patients.