Jackson S, Kler R S, Bartlett K, Briggs H, Bindoff L A, Pourfarzam M, Gardner-Medwin D, Turnbull D M
Division of Clinical Neuroscience, Medical School, University of Newcastle upon Tyne, United Kingdom.
J Clin Invest. 1992 Oct;90(4):1219-25. doi: 10.1172/JCI115983.
A young girl presented with recurrent episodes of muscle weakness culminating in a severe attack of generalized muscle weakness. In the muscle mitochondria from the patient there was an abnormal pattern of intermediates of beta-oxidation with an accumulation of 3-hydroxyacyl- and 2-enoyl-CoA and carnitine esters, and 3-oxoacylcarnitines. There was low activity of long-chain 3-hydroxyacyl-CoA dehydrogenase in mitochondria from all tissues. The activity of long-chain 2-enoyl-CoA hydratase was low in muscle mitochondria and 3-oxoacyl-CoA thiolase activity measured with 3-oxohexadecanoyl-CoA as substrate was low in fibroblast, muscle, and cardiac mitochondria but only partial deficiency was present when the activity was measured with 3-oxooctanoyl-CoA. The activity of the long-chain 3-hydroxyacyl-CoA dehydrogenase and long-chain 3-oxoacyl-CoA thiolase in fibroblasts from the patient's parents was intermediate between those of controls and the patient. The patient has a combined defect of the long-chain 3-hydroxyacyl-CoA dehydrogenase, long-chain 3-oxoacyl-CoA thiolase, and long-chain 2-enoyl-CoA hydratase which appears to be inherited in an autosomal recessive manner. This suggests there is a multifunctional enzyme catalyzing these activities in human mitochondria and that this enzyme is deficient in our patient.
一名年轻女孩反复出现肌肉无力症状，最终发展为严重的全身肌肉无力发作。在该患者的肌肉线粒体中，β-氧化中间体呈现异常模式，3-羟基酰基-CoA、2-烯酰基-CoA和肉碱酯以及3-氧代酰基肉碱积聚。所有组织线粒体中的长链3-羟基酰基-CoA脱氢酶活性均较低。肌肉线粒体中的长链2-烯酰基-CoA水合酶活性较低，以3-氧代十六烷酰-CoA为底物时，成纤维细胞、肌肉和心脏线粒体中的3-氧代酰基-CoA硫解酶活性较低，但以3-氧代辛酰-CoA为底物测量活性时仅存在部分缺陷。患者父母成纤维细胞中的长链3-羟基酰基-CoA脱氢酶和长链3-氧代酰基-CoA硫解酶活性介于对照组和患者之间。该患者存在长链3-羟基酰基-CoA脱氢酶、长链3-氧代酰基-CoA硫解酶和长链2-烯酰基-CoA水合酶的联合缺陷，似乎以常染色体隐性方式遗传。这表明在人类线粒体中存在一种催化这些活性的多功能酶，而我们的患者缺乏这种酶。
