LATE-ONSET RIBOFLAVIN-RESPONSIVE MYOPATHY WITH COMBINED MULTIPLE ACYL-COENZYME-A DEHYDROGENASE AND RESPIRATORY-CHAIN DEFICIENCY
LATE-ONSET RIBOFLAVIN-RESPONSIVE MYOPATHY WITH COMBINED MULTIPLE ACYL-COENZYME-A DEHYDROGENASE AND RESPIRATORY-CHAIN DEFICIENCY
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DOI：
10.1212/wnl.44.11.2153
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发表时间：
1994-11-01
期刊：
影响因子：
9.9
通讯作者：
DIDONATO, S
中科院分区：
文献类型：
--
作者：
ANTOZZI, C;GARAVAGLIA, B;DIDONATO, S
我们研究了核黄素治疗对一位69岁晚发性肌病患者临床状态、β-氧化和呼吸链酶活性的影响。治疗前，她四肢和躯干肌肉非常虚弱，虚弱，不能走路，也不能参加日常活动。肌肉活检中有明显的脂肪储存。肌肉线粒体中的短链酰基辅酶A脱氢酶(SCAD)、中链酰基辅酶A脱氢酶(MCAD)和长链酰基辅酶A脱氢酶(LCAD)的活性均降至对照的10%以下。脂肪酸氧化的这种缺陷与两个黄素依赖的呼吸链复合体的明显缺陷有关：复合体I的活性是对照组的20%，复合体II的活性是对照组的25%。相比之下，非黄素依赖的复合体III和复合体IV的活性是正常的。对患者肌肉线粒体提取物与纯化的SCAD、MCAD以及电子转移黄素蛋白(ETF)的α和β亚基抗体进行的Western印迹分析显示，没有SCAD交叉反应物质(CRM)，MCAD-CRM显著减少，α-和β-ETF-CRM均正常。核黄素治疗后，患者的临床状态显著改善，肌肉的形态变化消失。SCAD活性增加到控制值的55%，而MCAD、LCAD以及复合体I和复合体II的活性恢复正常。SCAD和MCAD免疫反应恢复正常。根据我们的经验和文献中的数据，我们得出结论，一些脂肪沉积性肌病对核黄素可以表现出显著的反应。
We studied the effect of riboflavin treatment on the clinical status and on the activities of beta-oxidation and respiratory chain enzymes in a 69-year-old patient with late-onset myopathy. Before treatment, she was very weak and wasted in the limbs and trunk muscles; also, she could not walk or attend to daily activities. Marked lipid storage was present in the muscle biopsy. The activities of short-chain acyl coenzyme A (acyl-CoA) dehydrogenase (SCAD), medium-chain acyl-CoA dehydrogenase (MCAD), and long-chain acyl-CoA dehydrogenase (LCAD) in isolated muscle mitochondria were reduced to less than 10% of control values. This defect in fatty acid oxidation was associated with a marked deficiency of two flavin-dependent respiratory chain complexes: complex I activity was 20% and complex II activity was 25% of control values. By contrast, the activities of the nonflavin-dependent complex III and complex IV were normal. Western blot analysis of the patient's muscle mitochondrial extracts with antibodies raised against purified SCAD, MCAD, and the alpha- and beta-subunits of the electron transfer flavoprotein (ETF) showed absence of SCAD crossreacting material (CRM), markedly decreased MCAD-CRM, and normal amounts of both alpha- and beta-ETF-CRM. After riboflavin treatment, the patient's clinical status dramatically improved and morphologic changes in muscle disappeared. SCAD activity increased to 55% of control values, whereas MCAD, LCAD, and complex I and complex II activities normalized. SCAD and MCAD immunoreactivity was restored to normal. On the basis of our experience and the data in the literature, we concluded that some lipid storage myopathies can show dramatic response to riboflavin.