儿童线粒体病伴发的肥厚型心肌病
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摘要
线粒体病是由于线粒体能量代谢异常而导致的一组遗传性疾病。心脏是线粒体病常见受累的器官之一,肥厚型心肌病(HCM)是线粒体病合并心脏受累最主要的类型。在线粒体病患者中,儿童期起病者合并HCM较成人期起病者更常见。合并心脏受累的线粒体病患儿,其病死率明显高于未合并心脏受累的患儿,因此,早期诊断和治疗非常重要。但目前由于线粒体病临床表现的复杂性,早期诊断仍较为困难。目前尚无针对线粒体病及其伴发的HCM的特异性治疗方法,主要为支持性治疗。
Mitochondrial disease is a heterogeneous group of hereditary diseases caused by the defects in the mitochondrial respiratory chain and abnormal cellular energy metabolism.Heart is one of the most common organs involved,and hypertrophic cardiomyopathy is the most common and important type of cardiac involvement in mitochondrial disease. Hypertrophic cardiomyopathy in the patients with mitochondrial disease with childhood onset is more common than those with adulthood onset. Mortality in children with cardiac involvement caused by mitochondrial disease is significantly higher than that in children without cardiac involvement,so the early diagnosis and treatment is very important. But the early diagnosis is still difficult due to the complexity of clinical manifestations of mitochondrial disease. There is no specific treatment for mitochondrial disease and its associated hypertrophic cardiomyopathy,so supportive therapy is still the main treatment.
Mitochondrial disease is a heterogeneous group of hereditary diseases caused by the defects in the mitochondrial respiratory chain and abnormal cellular energy metabolism.Heart is one of the most common organs involved,and hypertrophic cardiomyopathy is the most common and important type of cardiac involvement in mitochondrial disease. Hypertrophic cardiomyopathy in the patients with mitochondrial disease with childhood onset is more common than those with adulthood onset. Mortality in children with cardiac involvement caused by mitochondrial disease is significantly higher than that in children without cardiac involvement,so the early diagnosis and treatment is very important. But the early diagnosis is still difficult due to the complexity of clinical manifestations of mitochondrial disease. There is no specific treatment for mitochondrial disease and its associated hypertrophic cardiomyopathy,so supportive therapy is still the main treatment.
引文
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[15]Lev D,Nissenkorn A,Leshinsky-Silver E,et al.Clinical presentations of mitochondrial cardiomyopathies[J].Pediatr Cardiol,2004,25(5):443-450
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[17]Scaglia F,Towbin JA,Craigen WJ,et al.Clinical spectrum,morbidity,and mortality in 113 pediatric patients with mitochondrial disease[J].Pediatrics,2004,114(4):925-931.
[18]Finsterer J,Kothari S.Cardiac manifestations of primary mitochondrial disorders[J].Int J Cardiol,2014,177(3):754-763.
[19]Yaplito-Lee J,Weintraub R,Jamsen K,et al.Cardiac manifestations in oxidative phosphorylation disorders of childhood[J].J Pediatr,2007,150(4):407-411.
[20]张丽华,方理刚,程中伟,等.回顾性调查线粒体疾病患者的心脏病变[J].中华心血管病杂志,2009,37(10):892-895.
[21]Limongelli G,Tome-Esteban M,Dejthevaporn C,et al.Prevalence and natural history of heart disease in adults with primary mitochondrial respiratory chain disease[J].Eur J Heart Fail,2010,12(2):114-121.
[22]Yajima N,Yazaki Y,Yoshida K,et al.A case of mitochondrial cardiomyopathy with pericardial effusion evaluated by(99m)TcMIBI myocardial scintigraphy[J].J Nucl Cardiol,2009,16(6):989-994.
[23]Wortmann SB,Champion MP,van den Heuvel L,et al.Mitochondrial DNA m.3242G>A mutation,an under diagnosed cause of hypertrophic cardiomyopathy and renal tubular dysfunction?[J].Eur J Med Genet,2012,55(10):552-556.
[24]Okajima Y,Tanabe Y,Takayanagi M,et al.A follow-up study of myocardial involvement in patients with mitochondrial encephalomyopathy,lactic acidosis,and stroke-like episodes(MELAS)[J].Heart,1998,80(3):292-295.
[25]Spirito P,Autore C,Rapezzi C,et al.Syncope and risk of sudden death in hypertrophic cardiomyopathy[J].Circulation,2009,119(13):1703-1710.
[26]Colan SD,Lipshultz SE,Lowe AM,et al.Epidemiology and cause-specific outcome of hypertrophic cardiomyopathy in children:findings from the Pediatric Cardiomyopathy Registry[J].Circulation,2007,115(6):773-781.
[27]Gersh BJ,Maron BJ,Bonow RO,et al.2011 ACCF/AHA guideline for the diagnosis and treatment of hypertrophic cardiomyopathy:executive summary:a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines[J].Circulation,2011,124(6):2761-2796.
[28]Dominic EA,Ramezani A,Anker SD,et al.Mitochondrial cytopathies and cardiovascular disease[J].Heart,2014,100(8):611-618.
[29]Pfeffer G,Mezei MM.Cardiac screening investigations in adultonset progressive external ophthalmoplegia patients[J].Muscle Nerve,2012,46(4):593-596.
[30]Florian A,Ludwig A,Stubbe-Dr?ger B,et al.Characteristic cardiac phenotypes are detected by cardiovascular magnetic resonance in patients with different clinical phenotypes and genotypes of mitochondrial myopathy[J].J Cardiovasc Magn Reson,2015,17(22):40-50.
[31]Bates MG,Bourke JP,Giordano C,et al.Cardiac involvement in mitochondrial DNA disease:clinical spectrum,diagnosis,and management[J].Eur Heart J,2012,33(24):3023-3033.
[32]Koopman WJ,Willems PH,Smeitink JA.Monogenic mitochondrial disorders[J].N Engl J Med,2012,366(12):1132-1141.
[33]Veselka J,Anavekar NS,Charron P.Hypertrophic obstructive cardiomyopathy[J].Lancet,2017,389(10075):1253-1267.
[2]齐建光,张英,戚豫,等.儿童线粒体病心脏损害23例临床分析[J].中华实用儿科临床杂志,2006,21(1):12-13.
[3]Hsu YH,Yogasundaram H,Parajuli N,et al.MELAS syndrome and cardiomyopathy:linking mitochondrial function to heart failure pathogenesis[J].Heart Fail Rev,2016,21(1):103-116.
[4]Bates MGD,Bourke JP,Giordano C,et al.Cardiac involvement in mitochondrial DNA disease:clinical spectrum,diagnosis,and management[J].Eur Heart J,2012,33(24):3023-3033.
[5]Wahbi K,Larue S,Jardel C,et al.Cardiac involvement is frequent in patients with the m.8344A>G mutation of mitochondrial DNA[J].Neurology,2010,74(8):674-677.
[6]诸葛瑞琪,周荣,倪新海.线粒体心肌病分子遗传学机制的研究进展[J].中国医学科学院学报,2017,39(3):438-444.
[7]Brunel-Guitton C,Levtova A,Sasarman F.Mitochondrial diseases and cardiomyopathies[J].Can J Cardiol,2015,31(11):1360-1376.
[8]Lee SR,Han J.Mitochondrial mutations in cardiac disorders[M]//Santulli G.Mitochondrial dynamics in cardiovascular medicine.Norwich,United Kingdom:Springer International Publishing,2017:83-87.
[9]Elliott HR,Samuels DC,Eden JA,et al.Pathogenic mitochondrial DNA mutations are common in the general population[J].Am J Hum Genet,2008,83(2):254-260.
[10]Chinnery PF,Elliott HR,Hudson G,et al.Epigenetics,epidemiology and mitochondrial DNA diseases[J].Int J Epidemiol,2012,41(1):177-187.
[11]McBride HM,Neuspiel M,Wasiak S.Mitochondria:more than just a powerhouse[J].Curr Biol,2006,16(4):R551-R560.
[12]Gallagher D,Belmonte D,Deurenberg P,et al.Organ-tissue mass measurement allows modeling of REE and metabolically active tissue mass[J].Am J Physiol,1998,275(2Pt1):E249-E258.
[13]Akavia UD,Veinblat O,Benayahu D.Comparing the transcriptional profile of mesenchymal cells to cardiac and skeletal muscle cells[J].J Cell Physiol,2008,216(3):663-672.
[14]Limongelli G,Masarone D,D’Alessandro R,et al.Mitochondrial diseases and the heart:an overview of molecular basis,diagnosis,treatment and clinical course[J].Future Cardiol,2012,8(1):71-88.
[15]Lev D,Nissenkorn A,Leshinsky-Silver E,et al.Clinical presentations of mitochondrial cardiomyopathies[J].Pediatr Cardiol,2004,25(5):443-450
[16]Holmgren D,Wahlander H,Eriksson BO,et al.Cardiomyopathy in children with mitochondrial disease;clinical course and cardiological findings[J].Eur Heart J,2003,24(3):280-288.
[17]Scaglia F,Towbin JA,Craigen WJ,et al.Clinical spectrum,morbidity,and mortality in 113 pediatric patients with mitochondrial disease[J].Pediatrics,2004,114(4):925-931.
[18]Finsterer J,Kothari S.Cardiac manifestations of primary mitochondrial disorders[J].Int J Cardiol,2014,177(3):754-763.
[19]Yaplito-Lee J,Weintraub R,Jamsen K,et al.Cardiac manifestations in oxidative phosphorylation disorders of childhood[J].J Pediatr,2007,150(4):407-411.
[20]张丽华,方理刚,程中伟,等.回顾性调查线粒体疾病患者的心脏病变[J].中华心血管病杂志,2009,37(10):892-895.
[21]Limongelli G,Tome-Esteban M,Dejthevaporn C,et al.Prevalence and natural history of heart disease in adults with primary mitochondrial respiratory chain disease[J].Eur J Heart Fail,2010,12(2):114-121.
[22]Yajima N,Yazaki Y,Yoshida K,et al.A case of mitochondrial cardiomyopathy with pericardial effusion evaluated by(99m)TcMIBI myocardial scintigraphy[J].J Nucl Cardiol,2009,16(6):989-994.
[23]Wortmann SB,Champion MP,van den Heuvel L,et al.Mitochondrial DNA m.3242G>A mutation,an under diagnosed cause of hypertrophic cardiomyopathy and renal tubular dysfunction?[J].Eur J Med Genet,2012,55(10):552-556.
[24]Okajima Y,Tanabe Y,Takayanagi M,et al.A follow-up study of myocardial involvement in patients with mitochondrial encephalomyopathy,lactic acidosis,and stroke-like episodes(MELAS)[J].Heart,1998,80(3):292-295.
[25]Spirito P,Autore C,Rapezzi C,et al.Syncope and risk of sudden death in hypertrophic cardiomyopathy[J].Circulation,2009,119(13):1703-1710.
[26]Colan SD,Lipshultz SE,Lowe AM,et al.Epidemiology and cause-specific outcome of hypertrophic cardiomyopathy in children:findings from the Pediatric Cardiomyopathy Registry[J].Circulation,2007,115(6):773-781.
[27]Gersh BJ,Maron BJ,Bonow RO,et al.2011 ACCF/AHA guideline for the diagnosis and treatment of hypertrophic cardiomyopathy:executive summary:a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines[J].Circulation,2011,124(6):2761-2796.
[28]Dominic EA,Ramezani A,Anker SD,et al.Mitochondrial cytopathies and cardiovascular disease[J].Heart,2014,100(8):611-618.
[29]Pfeffer G,Mezei MM.Cardiac screening investigations in adultonset progressive external ophthalmoplegia patients[J].Muscle Nerve,2012,46(4):593-596.
[30]Florian A,Ludwig A,Stubbe-Dr?ger B,et al.Characteristic cardiac phenotypes are detected by cardiovascular magnetic resonance in patients with different clinical phenotypes and genotypes of mitochondrial myopathy[J].J Cardiovasc Magn Reson,2015,17(22):40-50.
[31]Bates MG,Bourke JP,Giordano C,et al.Cardiac involvement in mitochondrial DNA disease:clinical spectrum,diagnosis,and management[J].Eur Heart J,2012,33(24):3023-3033.
[32]Koopman WJ,Willems PH,Smeitink JA.Monogenic mitochondrial disorders[J].N Engl J Med,2012,366(12):1132-1141.
[33]Veselka J,Anavekar NS,Charron P.Hypertrophic obstructive cardiomyopathy[J].Lancet,2017,389(10075):1253-1267.