Tang Zhenchu, Gao Shan, He Miao, Chen Qihua, Fang Jia, Luo Yingying, Yan Weiqian, Shi Xiaoliu, Huang Hui, Tang Jianguang
Department of Neurology, Second Xiangya Hospital, Central South University, Changsha, China.
Hunan Key Laboratory of Tumor Models and Individualized Medicine, Second Xiangya Hospital, Central South University, Changsha, China.
Front Neurol. 2021 Nov 8;12:747360. doi: 10.3389/fneur.2021.747360. eCollection 2021.
Late-onset multiple acyl-CoA dehydrogenase deficiency (LO-MADD) describes a curable autosomal recessive genetic disease caused by mutations that result in defects in ETF-ubiquinone oxidoreductase. Almost all patients are responsive to riboflavin. This study describes the clinical presentations and genetic characteristics of five LO-MADD patients. From 2018 to 2021, we collected clinical and genetic data on five patients diagnosed with LO-MADD at our hospital and retrospectively analyzed their clinical characteristics, laboratory examination, electromyography, muscle biopsy, genetic analysis, and outcome data. This study included three males and two females with mean onset age of 37.8 years. Fluctuating exercise intolerance was the most common presentation. Serum creatine kinase (CK) levels were significantly elevated in all patients, and plasma acylcarnitine profiles revealed an increase in long-chain acylcarnitine species in three cases. The urinary organic acid study revealed a high level of hydroxyglutaric acid in all patients. Electrophysiology demonstrated myogenic impairment. Muscle biopsies revealed lipid storage myopathy. Molecular analysis identified nine mutations (three novels and six reported) in . Exercise intolerance and muscle weakness were dramatically improved in all patients treated with riboflavin (100 mg) daily following diagnosis. LO-MADD is caused by variants and responds well to riboflavin. Three novel pathogenic variants were identified, expanding their spectrum in the Chinese population and facilitating future interpretation and analysis of mutations.
迟发性多种酰基辅酶A脱氢酶缺乏症（LO-MADD）是一种可治愈的常染色体隐性遗传病，由导致电子传递黄素蛋白-泛醌氧化还原酶缺陷的突变引起。几乎所有患者对核黄素都有反应。本研究描述了5例LO-MADD患者的临床表现和基因特征。2018年至2021年，我们收集了我院确诊为LO-MADD的5例患者的临床和基因数据，并回顾性分析了他们的临床特征、实验室检查、肌电图、肌肉活检、基因分析及转归数据。本研究纳入3例男性和2例女性，平均发病年龄为37.8岁。运动不耐受波动是最常见的表现。所有患者血清肌酸激酶（CK）水平均显著升高，3例患者血浆酰基肉碱谱显示长链酰基肉碱种类增加。尿有机酸研究显示所有患者的羟基戊二酸水平升高。电生理学显示为肌源性损害。肌肉活检显示脂质贮积性肌病。分子分析在……中鉴定出9个突变（3个新突变和6个已报道突变）。所有确诊后每日接受核黄素（100mg）治疗的患者运动不耐受和肌无力均显著改善。LO-MADD由……变异引起，对核黄素反应良好。鉴定出3个新的致病变异，扩大了其在中国人群中的谱，便于未来对……突变的解释和分析。
