作者@article {engelstadp4.6 - 061 = {Kristin Engelstad和蕾切尔萨拉查和多加专门处理和苏珊Brodlie妮可拉马卡和艾琳Stackowitz Darryl De Vivo}, title ={探索Triheptanoin作为治疗短链Enoyl辅酶a水合酶缺乏症(p4.6 - 061)},体积={92}={15}补充数量,elocation-id = {p4.6 - 061} ={2019},出版商= {Wolters Kluwer健康,公司代表美国神经病学学会},文摘={目的:探讨Triheptanoin作为治疗短链的好处Enoyl Co-A水合酶(ECHS1)缺乏由于复合的杂合突变(p。首页Ala173Val ECHS1基因和p.Gly175Ser)。背景:ECHS1催化第二步的短链脂肪酸氧化(FAO)。粮农组织和异亮氨酸中间体据说是正常的。然而,缬氨酸升高中间体,methacrylyl和丙烯酰辅酶a,被认为损害丙酮酸脱氢酶复合体和电子传递链。只有少数病例报告。所有遭受全球脑病,严重的发育迟缓,大多数死于婴儿或儿童早期。没有有效的治疗方法。Triheptanoin是中链甘油三酸酯(C7石油),代谢庚酸和C4 / C5酮体。C7石油是一个补充的anaplerotic代理柠檬酸循环中间体形成乙酰辅酶a和丙酰辅酶a,随后草酰乙酸代谢。乙酰辅酶a和草酰乙酸凝结形成柠檬酸。Design/Methods: The patient presented at age 6 months with Leigh syndrome, global developmental delay, ptosis, oscillatory eye movements, mixed tone abnormalities, hyperreflexia and bilateral Babinski signs. The brain MRI scan demonstrated signal abnormalities in subcortical nuclei. At age 46 months, triheptanoin was administered enterally as an ascending dose (5\% to 35\% of total daily calories), using an approved individual patient IND. Safety measures (blood and urine chemistries, EKG), neurological and physical examinations and motor function assessments (CHOP-INTEND and GMFM-88) were performed quarterly.Results: The patient has been stable clinically with subtle improvements in awareness, posture, purposeful movements, mood and sleep pattern during 12 months of treatment. CHOP-INTEND improved 8 points (baseline 34/64; 12 month 42/64); and the GMFM-88 improved 14 points (baseline 9/264; 12 month 23/ 264). CNS score improved 8 points (baseline 42/76; 12 month 50/76). The drug has been well tolerated with no evidence of regression or serious side effects.Conclusions: Triheptanoin may be useful in the treatment of ECHS1D.Disclosure: Dr. Engelstad has nothing to disclose. Dr. Salazar has received research support from SMA Foundation, Biogen, Roche, AveXis, Mallinckrodt, Ultragenyx, PTC Therapeutics, Sarepta Therapeutics, and the Jain Foundation. Dr. Koenigsberger has nothing to disclose. Dr. Brodlie has nothing to disclose. Dr. La Marca has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, AveXis, Inc., PTC Therapeutics, and Sarepta Therapeutics. Dr. La Marca has received research support from Biogen, AveXis, Inc., Roche, PTC Therapeutics, and Sarepta Therapeutics. Dr. Stackowitz has nothing to disclose. Dr. De Vivo has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Advisor/consultant for AveXis, Biogen, Cytokinetics, Ionis Pharmaceuticals, Inc., Metafora, Roche, Sanofi, Sarepta, and the SMA Foundation. Dr. De Vivo has received research support from Grants from the Department of Defense, Hope for Children Research Foundation, the National Institutes of Health, and the SMA Foundation; clinical trials funding from Biogen, Mallinckrodt, PTC Therapeutics, Sarepta, and Ultragenyx.}, issn = {0028-3878}, URL = {//www.ez-admanager.com/content/92/15_Supplement/P4.6-061}, eprint = {//www.ez-admanager.com/content}, journal = {Neurology} }