线粒体呼吸链复合物Ⅱ缺陷所致Leigh综合征

马艳艳,吴桐菲,刘玉鹏,王峤,宋金青,肖江喜,姜玉武,杨艳玲

中国当代儿科杂志 ›› 2011, Vol. 13 ›› Issue (7) : 569-572.

PDF(1006 KB)
PDF(1006 KB)
中国当代儿科杂志 ›› 2011, Vol. 13 ›› Issue (7) : 569-572.
疑难病研究

线粒体呼吸链复合物Ⅱ缺陷所致Leigh综合征

  • 马艳艳,吴桐菲,刘玉鹏,王峤,宋金青,肖江喜,姜玉武,杨艳玲
作者信息 +

Leigh syndrome due to mitochondrial respiratory chain complex II deficiency

  • MA Yan-Yan, WU Tong-Fei, LIU Yu-Peng, WANG Jiao, SONG Jin-Qing, XIAO Jiang-Xi, JIANG Yu-Wu, YANG Yan-Ling
Author information +
文章历史 +

摘要

线粒体呼吸链复合物Ⅱ缺陷是较为少见的氧化磷酸化障碍性疾病。本文对1例单纯线粒体呼吸链复合物Ⅱ缺陷所致Leigh综合征患儿的诊疗进行回顾性分析。患儿,男,10个月,8个月时出现发热,热退后出现进行性全身无力、运动发育倒退和吞咽困难。血乳酸、丙酮酸增高,脑MRI显示双侧基底节对称性损害。对患儿进行了外周血白细胞线粒体氧化磷酸化酶复合物I-V活性测定和线粒体基因突变位点筛查分析。线粒体呼吸链复合物Ⅱ活性为21.9 nmol/min?mg线粒体总蛋白(正常对照47.3±5.3 nmol/min?mg线粒体总蛋白),柠檬酸合酶活性为22.1%(正常对照50.9%±10.7%),均显著降低。线粒体基因分析未发现异常。患儿确诊为线粒体呼吸链复合物Ⅱ缺陷所致Leigh综合征。经治疗患儿运动功能明显恢复。目前患儿22个月,病情稳定。

Abstract

Mitochondrial respiratory chain complex II deficiency is a rare documented cause of mitochondrial diseases. This study reported a case of Leigh syndrome due to isolated complex II deficiency. A boy presented with progressive weakness, motor regression and dysphagia after fever from the age of 8 months and hospitalized at the age of 10 months. Elevated blood levels of lactate and pyruvate were observed. Brain magnetic resonance image showed symmetrical lesions in the basal ganglia. Mitochondrial respiratory chain complex I-V activities in peripheral leukocytes were measured using spectrophotometric assay. Mitochondrial gene screening of common point mutations was performed. The complex II activity in the peripheral leukocytes decreased to 21.9 nmol/min per mg mitochondrial protein (control: 47.3±5.3 nmol/min per mg mitochondrial protein). The ratio of complex II activity to citrate synthase activity (22.1%) also decreased (control: 50.9%±10.7 %). No point mutation was found in mitochondrial DNA. The boy was diagnosed as Leigh syndrome due to isolated complex II deficiency. Psychomotor improvements were observed after the treatment. The patient is 22 months old and in a stable condition.

关键词

Leigh综合征 / 线粒体 / 线粒体呼吸链复合物Ⅱ缺陷 / 线粒体氧化磷酸化 / 儿童

Key words

Leigh syndrome / Mitochondria / Mitochondrial complex II deficiency / Oxidative phosphorylation / Child

引用本文

导出引用
马艳艳,吴桐菲,刘玉鹏,王峤,宋金青,肖江喜,姜玉武,杨艳玲. 线粒体呼吸链复合物Ⅱ缺陷所致Leigh综合征[J]. 中国当代儿科杂志. 2011, 13(7): 569-572
MA Yan-Yan, WU Tong-Fei, LIU Yu-Peng, WANG Jiao, SONG Jin-Qing, XIAO Jiang-Xi, JIANG Yu-Wu, YANG Yan-Ling. Leigh syndrome due to mitochondrial respiratory chain complex II deficiency[J]. Chinese Journal of Contemporary Pediatrics. 2011, 13(7): 569-572
中图分类号: R589   

参考文献

[1]Skladal D, Halliday J, Thorburn DR. Minimum birth prevalence of mitochondrial respiratory chain disorders in children[J]. Brain, 2003, 126(Pt 8): 1905-1912.

[2]Schaefer AM, Taylor RW, Turnbull DM, Chinnery PF. The epidemiology of mitochondrial disorders-past, present and future[J]. Biochim Biophys Acta, 2004, 1659(2-3): 115-120.

[3]Yang YL, Sun F, Zhang Y, Qian N, Yuan Y, Wang ZX, et al. Clinical and laboratory survey of 65 Chinese patients with Leigh syndrome[J]. Chin Med J (Engl), 2006, 119(5): 373-377.

[4]Zhang Y, Yang YL, Sun F, Cai X, Qian N, Yuan Y, et al. Clinical and molecular survey in 124 Chinese patients with Leigh or Leigh-like syndrome[J]. J Inherit Metab Dis, 2007, 30(2): 265.

[5]孙芳, 杨艳玲, 戚豫, 王朝霞, 袁云, 宋金青, 等. SURF1基因604G→C杂合性错义突变所致Leigh综合征患儿的临床与分子遗传学研究[J]. 中华神经科杂志,2005,38(9): 560-564.

[6]魏晓琼, 孔庆鹏, 张尧, 杨艳玲, 常杏芝, 戚豫, 等. 线粒体基因13513G>A突变导致呼吸链酶复合物I缺陷Leigh综合征[J]. 中国当代儿科杂志, 2009, 11(5): 333-336.

[7]Lemos RS, Fernandes AS, Pereira MM, Gomes CM, Teixeira M. Quinol:fumarate oxidoreductases and succinate:quinone oxidoreductases: phylogenetic relationships, metal centres and membrane attachment[J]. Biochim Biophys Acta, 2002, 1553(1-2): 158-170.

[8]Bourgeron T, Rustin P, Chretien D, BirchMachin M, Bourgeois M, Viegas-Péquignot E, et al. Mutation of a nuclear succinate dehydrogenase gene results in mitochondrial respiratory chain deficiency[J]. Nat Genet, 1995, 11(2): 144-149.

[9]Parfait B, Chretien D, Rotig A, Marsac C, Munnich A, Rustin P. Compound heterozygous mutations in the flavoprotein gene of the respiratory chain complex II in a patient with Leigh syndrome[J]. Hum Genet, 2000, 106(2): 236-243.

[10]van Coster R, Seneca S, Smet J, Van Hecke R, Gerlo E, Devreese B, et al. Homozygous Gly555Glu mutation in the nuclear-encoded 70 kDa flavoprotein gene causes instability of the respiratory chain complex II[J]. Am J Med Genet A, 2003, 120A(1):13-18.

[11]Ghezzi D, Goffrini P, Uziel G, Horvath R, Klopstock T, Lochmuller H, et al. SDHAF1, encoding a LYR complex-II specific assembly factor, is mutated in SDH-defective infantile leukoencephalopathy[J]. Nat Genet, 2009, 41(6):654-656.

[12]Kolker S, Schwab M, Horster F, Sauer S, Hinz A, Wolf NI, et al. Methylmalonic acid, a biochemical hallmark of methylmalonic acidurias but no inhibitor of mitochondrial respiratory chain[J]. J Biol Chem, 2003, 278(48):47388-47393.

[13]Brockmann K, Bjornstad A, Dechent P, Korenke CG, Smeitink J, Trijbels JM, et al. Succinate in dystrophic white matter: a proton magnetic resonance spectroscopy finding characteristic for complex II deficiency[J]. Ann Neurol, 2002, 52(1):38-46.

[14]Burgeois M, Goutieres F, Chretien D, Rustin P, Munnich A, Aicardi J. Deficiency in complex II of the respiratory chain, presenting as a leukodystrophy in two sisters with Leigh syndrome[J]. Brain Dev, 1992, 14(6):404-408.

[15]Taylor RW, Birch-Machin MA, Schaefer J, Taylor L, Shakir R, Ackrell BA, et al. Deficiency of complex II of the mitochondrial respiratory chain in lateonset optic atrophy and ataxia[J]. Ann Neurol, 1996, 39(2):224-232.

[16]Horvath R, Abicht A, Holinski-Feder E, Laner A, Gempel K, Prokisch H, et al. Leigh syndrome caused by mutations in the flavoprotein (Fp) subunit of succinate dehydrogenase (SDHA)[J]. J Neurol Neurosurg Psychiatry, 2006, 77(1):74-76.

[17]Sugimoto J, Shimohira M, Osawa Y, Matsubara M, Yamamoto H, Goto Y, et al. A patient with mitochondrial myopathy associated with isolated succinate dehydrogenase deficiency[J]. Brain Dev, 2000, 22(3):158-162.

[18]Bugiani M, Lamantea E, Invernizzi F, Moroni I, Bizzi A, Zeviani M, et al. Effects of riboflavin in children with complex II deficiency[J]. Brain Dev, 2006, 28(9):576-581.

[19]Manthey KC, Rodriguez-Melendez R, Hoi JT, Zempleni J. Riboflavin deficiency causes protein and DNA damage in HepG2 cells, triggering arrest in G1 phase of the cell cycle[J]. J Nutr Biochem, 2006, 17(4):250-256.

[20]Di Rocco M, Lamba LD, Minniti G, Caruso U, Naito E. Outcome of thiamine treatment in a child with Leigh disease due to thiamine-responsive pyruvate dehydrogenase deficiency[J]. Eur J Paediatr Neurol, 2000, 4(3):115-117.

[21]Lou HC. Correction of increased plasma pyruvate and plasma lactate levels using large doses of thiamine in patients with Kearns-Sayre syndrome[J]. Arch Neurol, 1981, 38(7):469.

[22]杨艳玲, 宋金青, 孙芳, 张月华, 包新华, 钱宁, 等. 气相色谱-质谱联用分析在有机酸尿症筛查与诊断中的应用[J]. 中国医刊, 2006,41(2):38-40.

[23]顾学范, 韩连书, 高晓岚, 杨艳玲, 叶军, 邱文娟. 串联质谱技术在遗传性代谢病高危儿童筛查中的初步应用[J]. 中华儿科杂志, 2004, 42(06):401-404.

[24]Kimura M, Yamamoto T, Yamaguchi S. Automated metabolic profiling and interpretation of GC/MS data for organic acidemia screening: a personal computer-based system[J]. Tohoku J Exp Med, 1999, 188(4):317-334.

[25]王朝霞, 袁云, 陈清棠, 杨艳玲, 张月华, 戚豫. Leigh综合征的线粒体DNA突变分析[J]. 中华神经科杂志, 2003, 36(1):28-31.

[26]van den Heuvel L, Smeitink J. The oxidative phosphorylation (OXPHOS) system: nuclear genes and human genetic diseases[J]. Bioessays, 2001, 23(6):518-525.

[27]Rustin P, Bourgeron T, Parfait B, Chretien D, Munnich A, Rotig A. Inborn errors of the Krebs cycle: a group of unusual mitochondrial diseases in human[J]. Biochim Biophys Acta, 1997, 1361(2):185-197.

[28]Rivner MH, Shamsnia M, Swift TR, Trefz J, Roesel RA, Carter AL, et al. Kearns-Sayre syndrome and complex II deficiency[J]. Neurology, 1989, 39(5): 693-696.

[29]Chretien D, Rustin P, Bourgeron T, Rotig A, Saudubray JM, Munnich A. Reference charts for respiratory chain activities in human tissues[J]. Clin Chim Acta, 1994, 228(1): 53-70.

PDF(1006 KB)

Accesses

Citation

Detail

段落导航
相关文章

/