DiDonato S, Gellera C, Peluchetti D, Uziel G, Antonelli A, Lus G, Rimoldi M
Laboratory of Biochemistry and Genetics of the Nervous System, Instituto Neurologico C. Besta, Milan, Italy.
Ann Neurol. 1989 May;25(5):479-84. doi: 10.1002/ana.410250510.
A 12-year-old girl was shown to have carnitine-deficient lipid storage myopathy and organic aciduria compatible with multiple acylcoenzyme A (acyl-CoA) dehydrogenase deficiency. In muscle mitochondria, activities of both short-chain acyl-CoA dehydrogenase (SCAD) and medium-chain acyl-CoA dehydrogenase (MCAD) were 35% of normal. Antibodies against purified SCAD, MCAD, and electron-transfer flavoprotein were used for detection of cross-reacting material (CRM) in the patient's mitochondria. Western blot analysis showed absence of SCAD-CRM, reduced amounts of MCAD-CRM, and normal amounts of electron-transfer flavoprotein-CRM. The patient, who was unresponsive to treatment with oral carnitine, improved dramatically with daily administration of 100 mg oral riboflavin. Increase in muscle bulk and strength and resolution of the organic aciduria were associated with normalization of SCAD activity and "reappearance" of SCAD-CRM. In contrast, both MCAD activity and MCAD-CRM remained lower than normal. These results suggest that in some patients with multiple acyl-CoA dehydrogenase deficiency riboflavin supplementation may be effective in restoring the activity of SCAD, and possibly of other mitochondrial flavin-dependent enzymes.
一名12岁女孩被诊断患有肉碱缺乏性脂质贮积性肌病和与多种酰基辅酶A（酰基-CoA）脱氢酶缺乏症相符的有机酸尿症。在肌肉线粒体中，短链酰基辅酶A脱氢酶（SCAD）和中链酰基辅酶A脱氢酶（MCAD）的活性均为正常水平的35%。针对纯化的SCAD、MCAD和电子传递黄素蛋白的抗体用于检测患者线粒体中的交叉反应物质（CRM）。蛋白质印迹分析显示，患者线粒体中不存在SCAD-CRM，MCAD-CRM含量减少，而电子传递黄素蛋白-CRM含量正常。该患者对口服肉碱治疗无反应，但每天口服100毫克核黄素后病情显著改善。肌肉量和力量增加以及有机酸尿症消退与SCAD活性正常化和SCAD-CRM“重现”相关。相比之下，MCAD活性和MCAD-CRM仍低于正常水平。这些结果表明，在一些患有多种酰基辅酶A脱氢酶缺乏症的患者中，补充核黄素可能有效恢复SCAD以及其他线粒体黄素依赖性酶的活性。
