Treatment of cardiomyopathy and rhabdomyolysis in long-chain fat oxidation disorders using an anaplerotic odd-chain triglyceride.
Treatment of cardiomyopathy and rhabdomyolysis in long-chain fat oxidation disorders using an anaplerotic odd-chain triglyceride.
复制标题
使用回补奇数链甘油三酯治疗长链脂肪氧化障碍中的心肌病和横纹肌溶解症。
DOI：
10.1172/jci15311
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发表时间：
2002
期刊：
影响因子：
--
通讯作者：
Brunengraber,Henri
中科院分区：
文献类型：
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作者：
Roe,CharlesR;Sweetman,Lawrence;Roe,DianeS;David,France;Brunengraber,Henri
目前的饮食治疗长链脂肪酸氧化缺陷（高碳水化合物与中等甚至链甘油三酯和减少量的长链脂肪）失败，在许多情况下，以防止心肌病，横纹肌溶解症，肌无力。我们假设，在能源生产中的明显缺陷的结果从柠檬酸循环的催化中间体通过泄漏通过细胞膜（cataplerosis）耗尽。我们进一步假设，用中奇链脂肪酸（乙酰辅酶A和回补丙酰辅酶A的前体）替代膳食中偶链脂肪酸（乙酰辅酶A的前体）将恢复能量产生并改善心脏和骨骼肌功能。我们给有长链缺陷的受试者喂食控制饮食，其中脂肪成分从中-偶链甘油三酯转换为三庚酸甘油酯。在3例极长链酰基辅酶A脱氢酶缺乏症患者中，这种治疗迅速导致临床改善，包括慢性心肌病、横纹肌溶解和肌无力（1例儿童超过2年）的永久消失，以及其他儿童横纹肌溶解和肌无力的永久消失。在这些患者中没有丙酰基过载的证据。该治疗耐受性良好，长达26个月，为线粒体脂肪氧化障碍患者的管理开辟了新的途径。
The current dietary treatment of long-chain fatty acid oxidation defects (high carbohydrate with medium-even-chain triglycerides and reduced amounts of long-chain fats) fails, in many cases, to prevent cardiomyopathy, rhabdomyolysis, and muscle weakness. We hypothesized that the apparent defect in energy production results from a depletion of the catalytic intermediates of the citric acid cycle via leakage through cell membranes (cataplerosis). We further hypothesized that replacing dietary medium-even-chain fatty acids (precursors of acetyl-CoA) by medium-odd-chain fatty acids (precursors of acetyl-CoA and anaplerotic propionyl-CoA) would restore energy production and improve cardiac and skeletal muscle function. We fed subjects with long-chain defects a controlled diet in which the fat component was switched from medium-even-chain triglycerides to triheptanoin. In three patients with very-long-chain acyl-CoA dehydrogenase deficiency, this treatment led rapidly to clinical improvement that included the permanent disappearance of chronic cardiomyopathy, rhabdomyolysis, and muscle weakness (for more than 2 years in one child), and of rhabdomyolysis and weakness in the others. There was no evidence of propionyl overload in these patients. The treatment has been well tolerated for up to 26 months and opens new avenues for the management of patients with mitochondrial fat oxidation disorders.