脂肪酸氧化代谢病与心肌病
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摘要
脂肪酸是心肌最重要的能量来源,脂肪酸氧化代谢病(FAOD)可导致线粒体能量生成不足,同时可造成心肌细胞内脂质和长链酰基肉碱等中间代谢产物蓄积,从而导致心肌病变。FAOD主要包括肉碱依赖的脂肪酸转运障碍和线粒体内的脂肪酸β-氧化异常,缺陷可发生于脂肪酸氧化过程中的任何酶或转运蛋白。尽管FAOD是引起儿童心肌病的少见病因之一,但部分FAOD通过早期纠正脂肪酸代谢紊乱后,心肌病有望得到改善,生存质量可显著提高。
myocardium. Fatty acid oxidation disorders(FAODs)can give rise to insufficiency of mitochondrial energy production and accumulation of metabolic intermediates in cardiomyocytes,such as lipid and long-chain acyl carnitine,leading to myocardial lesions.FAODs include carnitine-dependent fatty acid transport disorders and mitochondrial fatty acid beta-oxidation disorders,with any enzyme or transporter defect in fatty acid oxidation process resulting in this disease. Although FAODs are one of the rare causes of pediatric cardiomyopathy,some patients with FAODs are expected to have cardiomyopathy alleviated and quality of life improved by early correction of fatty acid metabolic disorders.
myocardium. Fatty acid oxidation disorders(FAODs)can give rise to insufficiency of mitochondrial energy production and accumulation of metabolic intermediates in cardiomyocytes,such as lipid and long-chain acyl carnitine,leading to myocardial lesions.FAODs include carnitine-dependent fatty acid transport disorders and mitochondrial fatty acid beta-oxidation disorders,with any enzyme or transporter defect in fatty acid oxidation process resulting in this disease. Although FAODs are one of the rare causes of pediatric cardiomyopathy,some patients with FAODs are expected to have cardiomyopathy alleviated and quality of life improved by early correction of fatty acid metabolic disorders.
引文
[1]傅立军,陈浩.儿童遗传代谢性心肌病的诊断与治疗进展[J].中华实用儿科临床杂志,2018,33(13):965-969.
[2]El-Gharbawy A,Vockley J.Inborn errors of metabolism with myopathy:defects of fatty acid oxidation and the carnitine shuttle system[J].Pediatr Clin North Am,2018,65(2):317-335.
[3]Lopaschuk GD,Ussher JR,Folmes CD,et al.Myocardial fatty acid metabolism in health and disease[J].Physiol Rev,2010,90(1):207-258.
[4]Das AM,Steuerwald U,Illsinger S.Inborn errors of energy metabolism associated with myopathies[J].J Biomed Biotechnol,2010,2010:340849.
[5]Cox G.Diagnostic Approaches to pediatric cardiomyopathy of metabolic genetic etiologies and their relation to therapy[J].Prog Pediatr Cardiol,2007,24(1):15-25.
[6]Fu L,Huang M,Chen S.Primary carnitine deficiency and cardiomyopathy[J].Korean Circ J,2013,43(12):785-792.
[7]Wilcken B.Fatty acid oxidation disorders:outcome and long-term prognosis[J].J Inherit Metab Dis,2010,33(5):501-506.
[8]傅立军,陈树宝,韩连书,等.肉碱缺乏所致心肌病的临床特点及治疗随访[J].中华儿科杂志,2012,50(12):929-934.
[9]Rubio-Gozalbo ME,Bakker JA,Waterham HR,et al.Carnitineacylcarnitine translocase deficiency,clinical,biochemical and genetic aspects[J].Mol Aspects Med,2004,25(5-6):521-532.
[10]Vockley J,Charrow J,Ganesh J,et al.Triheptanoin treatment in patients with pediatric cardiomyopathy associated with long chain-fatty acid oxidation disorders[J].Mol Genet Metab,2016,119(3):223-231.
[11]Isackson PJ,Bennett MJ,Lichter-Konecki U,et al.CPT2 gene mutations resulting in lethal neonatal or severe infantile carnitine palmitoyltransferase II deficiency[J].Mol Genet Metab,2008,94(4):422-427.
[12]Olpin SE,Afifi A,Clark S,et al.Mutation and biochemical analysis in carnitine palmitoyltransferase typeⅡ(CPTⅡ)deficiency[J].J Inherit Metab Dis,2003,26(6):543-557.
[13]Andresen BS,Olpin S,Poorthuis BJ,et al.Clear correlation of genotype with disease phenotype in very-long-chain acyl-CoAdehydrogenase deficiency[J].Am J Hum Genet,1999,64(2):479-494.
[14]Xiong D,He H,James J,et al.Cardiac-specific VLCAD deficiency induces dilated cardiomyopathy and cold intolerance[J].Am J Physiol Heart Circ Physiol,2014,306(3):326-338.
[15]Vockley J,Marsden D,McCracken E,et al.Long-term major clinical outcomes in patients with long chain fatty acid oxidation disorders before and after transition to triheptanoin treatment-a retrospective chart review[J].Mol Genet Metab,2015,116(1-2):53-60.
[16]Labarthe F,Gélinas R,Des Rosiers C.Medium-chain fatty acids as metabolic therapy in cardiac disease[J].Cardiovasc Drugs Ther,2008,22(2):97-106.
[17]Olpin SE.Pathophysiology of fatty acid oxidation disorders and resultant phenotypic variability[J].J Inherit Metab Dis,2013,36(4):645-658.
[18]den Boer ME,Dionisi-Vici C,Chakrapani A,et al.Mitochondrial trifunctional protein deficiency:a severe fatty acid oxidation disorder with cardiac and neurologic involvement[J].J Pediatr,2003,142(6):684-689.
[19]Spiekerkoetter U,Lindner M,Santer R,et al.Treatment recommendations in long-chain fatty acid oxidation defects:consensus from a workshop[J].J Inherit Metab Dis,2009,32(4):498-505.
[20]Olsen RK,Olpin SE,Andresen BS,et al.ETFDH mutations as a major cause of riboflavin-responsive multiple acyl-CoA dehydrogenation deficiency[J].Brain,2007,130(Pt 8):2045-2054.
[21]Vasiljevski ER,Summers MA,Little DG,et al.Lipid storage myopathies:current treatments and future directions[J].Prog Lipid Res,2018,72(1):1-17.
[2]El-Gharbawy A,Vockley J.Inborn errors of metabolism with myopathy:defects of fatty acid oxidation and the carnitine shuttle system[J].Pediatr Clin North Am,2018,65(2):317-335.
[3]Lopaschuk GD,Ussher JR,Folmes CD,et al.Myocardial fatty acid metabolism in health and disease[J].Physiol Rev,2010,90(1):207-258.
[4]Das AM,Steuerwald U,Illsinger S.Inborn errors of energy metabolism associated with myopathies[J].J Biomed Biotechnol,2010,2010:340849.
[5]Cox G.Diagnostic Approaches to pediatric cardiomyopathy of metabolic genetic etiologies and their relation to therapy[J].Prog Pediatr Cardiol,2007,24(1):15-25.
[6]Fu L,Huang M,Chen S.Primary carnitine deficiency and cardiomyopathy[J].Korean Circ J,2013,43(12):785-792.
[7]Wilcken B.Fatty acid oxidation disorders:outcome and long-term prognosis[J].J Inherit Metab Dis,2010,33(5):501-506.
[8]傅立军,陈树宝,韩连书,等.肉碱缺乏所致心肌病的临床特点及治疗随访[J].中华儿科杂志,2012,50(12):929-934.
[9]Rubio-Gozalbo ME,Bakker JA,Waterham HR,et al.Carnitineacylcarnitine translocase deficiency,clinical,biochemical and genetic aspects[J].Mol Aspects Med,2004,25(5-6):521-532.
[10]Vockley J,Charrow J,Ganesh J,et al.Triheptanoin treatment in patients with pediatric cardiomyopathy associated with long chain-fatty acid oxidation disorders[J].Mol Genet Metab,2016,119(3):223-231.
[11]Isackson PJ,Bennett MJ,Lichter-Konecki U,et al.CPT2 gene mutations resulting in lethal neonatal or severe infantile carnitine palmitoyltransferase II deficiency[J].Mol Genet Metab,2008,94(4):422-427.
[12]Olpin SE,Afifi A,Clark S,et al.Mutation and biochemical analysis in carnitine palmitoyltransferase typeⅡ(CPTⅡ)deficiency[J].J Inherit Metab Dis,2003,26(6):543-557.
[13]Andresen BS,Olpin S,Poorthuis BJ,et al.Clear correlation of genotype with disease phenotype in very-long-chain acyl-CoAdehydrogenase deficiency[J].Am J Hum Genet,1999,64(2):479-494.
[14]Xiong D,He H,James J,et al.Cardiac-specific VLCAD deficiency induces dilated cardiomyopathy and cold intolerance[J].Am J Physiol Heart Circ Physiol,2014,306(3):326-338.
[15]Vockley J,Marsden D,McCracken E,et al.Long-term major clinical outcomes in patients with long chain fatty acid oxidation disorders before and after transition to triheptanoin treatment-a retrospective chart review[J].Mol Genet Metab,2015,116(1-2):53-60.
[16]Labarthe F,Gélinas R,Des Rosiers C.Medium-chain fatty acids as metabolic therapy in cardiac disease[J].Cardiovasc Drugs Ther,2008,22(2):97-106.
[17]Olpin SE.Pathophysiology of fatty acid oxidation disorders and resultant phenotypic variability[J].J Inherit Metab Dis,2013,36(4):645-658.
[18]den Boer ME,Dionisi-Vici C,Chakrapani A,et al.Mitochondrial trifunctional protein deficiency:a severe fatty acid oxidation disorder with cardiac and neurologic involvement[J].J Pediatr,2003,142(6):684-689.
[19]Spiekerkoetter U,Lindner M,Santer R,et al.Treatment recommendations in long-chain fatty acid oxidation defects:consensus from a workshop[J].J Inherit Metab Dis,2009,32(4):498-505.
[20]Olsen RK,Olpin SE,Andresen BS,et al.ETFDH mutations as a major cause of riboflavin-responsive multiple acyl-CoA dehydrogenation deficiency[J].Brain,2007,130(Pt 8):2045-2054.
[21]Vasiljevski ER,Summers MA,Little DG,et al.Lipid storage myopathies:current treatments and future directions[J].Prog Lipid Res,2018,72(1):1-17.