核黄素反应性脂质沉积性肌病的生化分析
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摘要
目的:
探讨核黄素反应性脂质沉积性肌病的临床、病理和生化特征,以及血尿生化指标和临床表现型间的关系。
方法:
19例患者为山东大学齐鲁医院神经肌肉病研究室病例,根据患者的临床、肌肉病理确诊。取患者尿、血标本分别行有机酸分析和脂酰肉碱分析,同时回顾性分析核黄素反应性LSM患者的临床特征和病理表现。
结果:
1.临床特点:亚急性起病的四肢近端和躯干肌无力,不能耐受疲劳。16例患者有颈肌无力,14例有明显的咀嚼肌无力。17例患者血清磷酸激酶(CK)轻度至中度升高。所有患者核黄素治疗均有显著效果。
2.肌肉病理特点:光镜下19例患者的肌纤维内均出现大量脂滴沉积,以Ⅰ型纤维为主。3例患者SDH酶活性缺失,3例患者MGT染色可见红纤维。
3.生化特点:13例患者发作期尿有机酸分析示11例戊二酸尿症Ⅱ型,19例患者血酰基肉碱分析示17例符合多种酰基辅酶A脱氢缺陷(MADD)。
结论:
本病多以四肢近端、颈肌、脊旁肌和咀嚼肌受累为主要表现,病理特征为肌纤维内大量脂肪沉积,核黄素单药治疗对本病有显著疗效。19例患者中17例生化分析支持MADD,表明MADD为我国RR-LSM患者主要病理机制。
Objective:
To clarify the clinical,pathological and biological features of riboflavin responsive lipid storage myopathy(RR-LSM).
Methods:
The clinical data and therapeutic effects of 19 LSM patients were summarize retrospectively.The clinical and pathological presentation confirmed RR-LSM definitely.All patients were subjected to urine oganic acids analysis and bloo acyl-camitine profile.
Results:
1.clinical data:
All patients were subacute onset.The proximal and trunk muscle weakness were the most common clinical features and exercise intolerance was also noticeable.Neck muscles Weakness were found in 16 cases,and chewing muscles were involved in 14 cases.17 patients displayed elevated plasma creatine kinase(CK) from sevral folds to 20 folds.All patients showed marked and quick improvement of symptoms after riboflavin therapy(15-150mg).
2.pathological feature:
Muscle Biopsy study showed marked increased lipid droplets in muscle fibers, predominantly in typeⅠfibers.On SDH,diffuse decreased activity of enzymatic activity was found in 3 patients.On MGT,several ragged red fibers(RRFs) were seen in 3 patients.
3.biological results:
Urine analysis revealed that 11 out of 13 samples collected during crisis were glutaric aciduria typeⅡ(GAⅡ),and blood acyl-camitine profile indicated that 17 out of 19 patients were multiple acyl-CoA dehydrogenation deficiency(MADD).
Conclusions:
LSM is characterized by preferential involvement of neck and trunck muscles. The distinct pathological feature is lipid accumulation in muscle fibers.Our data suggest that MADD(Glutaric aciduria typeⅡ) should take responsibility for our 17 LSM patients who are responsive to riboflavin,indicating RR-LSM is mainly due to MADD.
探讨核黄素反应性脂质沉积性肌病的临床、病理和生化特征,以及血尿生化指标和临床表现型间的关系。
方法:
19例患者为山东大学齐鲁医院神经肌肉病研究室病例,根据患者的临床、肌肉病理确诊。取患者尿、血标本分别行有机酸分析和脂酰肉碱分析,同时回顾性分析核黄素反应性LSM患者的临床特征和病理表现。
结果:
1.临床特点:亚急性起病的四肢近端和躯干肌无力,不能耐受疲劳。16例患者有颈肌无力,14例有明显的咀嚼肌无力。17例患者血清磷酸激酶(CK)轻度至中度升高。所有患者核黄素治疗均有显著效果。
2.肌肉病理特点:光镜下19例患者的肌纤维内均出现大量脂滴沉积,以Ⅰ型纤维为主。3例患者SDH酶活性缺失,3例患者MGT染色可见红纤维。
3.生化特点:13例患者发作期尿有机酸分析示11例戊二酸尿症Ⅱ型,19例患者血酰基肉碱分析示17例符合多种酰基辅酶A脱氢缺陷(MADD)。
结论:
本病多以四肢近端、颈肌、脊旁肌和咀嚼肌受累为主要表现,病理特征为肌纤维内大量脂肪沉积,核黄素单药治疗对本病有显著疗效。19例患者中17例生化分析支持MADD,表明MADD为我国RR-LSM患者主要病理机制。
Objective:
To clarify the clinical,pathological and biological features of riboflavin responsive lipid storage myopathy(RR-LSM).
Methods:
The clinical data and therapeutic effects of 19 LSM patients were summarize retrospectively.The clinical and pathological presentation confirmed RR-LSM definitely.All patients were subjected to urine oganic acids analysis and bloo acyl-camitine profile.
Results:
1.clinical data:
All patients were subacute onset.The proximal and trunk muscle weakness were the most common clinical features and exercise intolerance was also noticeable.Neck muscles Weakness were found in 16 cases,and chewing muscles were involved in 14 cases.17 patients displayed elevated plasma creatine kinase(CK) from sevral folds to 20 folds.All patients showed marked and quick improvement of symptoms after riboflavin therapy(15-150mg).
2.pathological feature:
Muscle Biopsy study showed marked increased lipid droplets in muscle fibers, predominantly in typeⅠfibers.On SDH,diffuse decreased activity of enzymatic activity was found in 3 patients.On MGT,several ragged red fibers(RRFs) were seen in 3 patients.
3.biological results:
Urine analysis revealed that 11 out of 13 samples collected during crisis were glutaric aciduria typeⅡ(GAⅡ),and blood acyl-camitine profile indicated that 17 out of 19 patients were multiple acyl-CoA dehydrogenation deficiency(MADD).
Conclusions:
LSM is characterized by preferential involvement of neck and trunck muscles. The distinct pathological feature is lipid accumulation in muscle fibers.Our data suggest that MADD(Glutaric aciduria typeⅡ) should take responsibility for our 17 LSM patients who are responsive to riboflavin,indicating RR-LSM is mainly due to MADD.
引文
[1]Wang Q.Z,Yan C.Z.,Wu J.L.,et al.Clinical and pathological characteristics of riboflavin.reactive lipid storage myopathy.Journal of Clinical Neurology 2005;18:357-359.
[2]Bradley WG,Hudgson P,Gardner-Medwin D,Walton JN.Myopathy associated with abnormal lipid metabolism in skeletal muscle.Lancet 1969;1:495-498.
[3]曹佩芝,吕丹云,夏谦,吴淑平.脂质沉积性肌病2例报告.中华神经精神科杂志 1990;4:216-218.
[4]李大年,刘淑萍,焉传祝,等.脂质沉积性肌病.临床神经病学杂志1995;8:73-75.
[5]王翠娣,殷剑,许贤豪,等.脂质沉积性肌病8例临床病理研究.中华病理学杂志2001;30:19-22.
[6]林红,王柠,慕容慎行,等.脂质沉积性肌病15例临床与病理分析.福建医科大学学报2000;34.
[7]狄晴,张平,张颖冬.脂质沉积性肌病临床及病理特点.临床神经病学杂志1998;11:280-282.
[8]姚璇,刘永海,许东升.脂质沉积性肌病6例临床分析.徐州医学院学报2000;20:163-164.
[9]吕海东,杨斌,秦东香,等.脂质沉积性肌病的临床与病理分析.实用神经疾病杂志2005;8:2-4.
[10]毕桂楠,梁莹,马朝桂.脂质沉积性肌病5例临床病理报道.广西医科大学学报1999;16:133.
[11]韩漫夫,赫秋月.肌活检诊断脂质沉积性肌病4例报道.中国实用内科杂志1999:19:632-633.
[12]Li W.,Yan C.Z.,Wu J.L.,et al.Therapeutic efects and long term follow-ups in 42case,s of ljpjd storage myopathy.Chin J Neur 2007;40:229-231.
[13]Gempel K,Topaloglu H,Talim B,et al.The myopathic form of coenzyme Q10deficiency is caused by mutations in the electron-transferring-flavoprotein dehydrogenase(ETFDH) gene.Brain 2007;130:2037-2044.
[14]Olsen RKJ,Pourfarzam M,Morris AAM,et al.Lipid-storage myopathy and respiratory insufficiency due to ETFQO mutations in a patient with late-onset multiple acyl-CoA dehydrogenation deficiency.Journal of Inherited Metabolic Disease 2004;27:671-678.
[15]Bressler R.Camitine and the twins.NEnglJMed 1970:745.
[16]Vielhaber S,Feistner H,Weis J,et al.Primary camitine deficiency:adult onset lipid storage myopathy with a mild clinical course.J Clin Neurosci 2004;11:919-924.
[17]Donato SD,Taroni F,editors,Myology,Basic and Clinical,the third edition,3 ed.New York:McGraw-Hill,2003.
[18]赵玉英,焉传祝.第62例-间歇性呕吐、进行性四肢无力.中华神经科杂志;41:61-63.
[19]Gordon N.Glutaric aciduria types Ⅰ and Ⅱ.Brain & Development 2006;28:136-140.
[20]杨艳玲,木村正彦,袁云,et al.戊二酸尿症Ⅱ型所致脂肪沉积性肌肉病的诊断与治疗分析.中华神经科杂志2004;5:438-441.
[21]梁雁,刘丽,魏虹,罗小平,王慕逖.维生素B2治疗有效的晚发型戊二酸尿症Ⅱ型.中华儿科杂志2003;12:916-920.
[22]Wanders RJ,Vreken P,den Boer ME,Wijburg FA,van Gennip AH,L IJ.Disorders of mitochondrial fatty acyl-CoA beta-oxidation.J Inherit Metab Dis 1999;22:442-487.
[23]Nezu J,Tamai I,Oku A,et al.Primary systemic camitine deficiency is caused by mutations in a gene encoding sodium ion-dependent camitine transporter.Nature genetics 1999;21:91-94.
[24]Iacobazzi V,Invemizzi F,Baratta S,et al.Molecular and functional analysis of SLC25A20 mutations causing carnitine-acylcamitine translocase deficiency.Hum Mutat 2004;24:312-320.
[25]Haap M,Thamer C,Machann J,et al.Metabolic characterization of a woman homozygous for the Ser113Leu missense mutation in carnitine palmitoyl transferase Ⅱ.The Journal of clinical endocrinology and metabolism 2002;87:2139-2143.
[26]李大年,现代神经内科学,1 ed.济南:山东科学技术出版社,2002.
[27]Angelini C,editor,Disorders of lipid metabolism,2007.
[28]Olsen RKJ,Olpin SE,Andresen BS,et al.ETFDH mutations as a major cause of riboflavin-responsive multiple acyl-CoA dehydrogenation deficiency.Brain 2007;130:2045-2054.
[29]Goodman SI,Binard RJ,Woontner MR,Frerman FE.Glutaricacidemia type Ⅱ:gene structure and mutations of the electron transfer flavoprotein:ubiquinone oxidoreductase(ETF:QO) gene.Molecular Genetics and Metabolism 2002:86-90.
[30]Tein I,Elpeleg O,Ben-Zeev B,et al.Short-chain acyl-CoA dehydrogenase gene mutation(c.319C ＞ T) presents with clinical heterogeneity and is candidate founder mutation in individuals of Ashkenazi Jewish origin.Molecular Genetics and Metabolism 2008;93:179-189.
[31]Tumbull DM,Bartlett K,Stevens DL,et al.Short-chain acyl-CoA dehydrogenase deficiency associated with a lipid-storage myopathy and secondary carnitine deficiency.The New England journal of medicine 1984;311:1232-1236.
[32]Aoyama T,Uchida Y,Kelley RI,et al.A novel disease with deficiency of mitochondrial very-long-chain acyl-CoA dehydrogenase.Biochem Biophys Res Commun 1993;191:1369-1372.
[33]Onkenhout W,Venizelos V,Scholte HR,De Klerk JB,Poorthuis BJ.Intermediates of unsaturated fatty acid oxidation are incorporated in triglycerides but not in phospholipids in tissues from patients with mitochondrial beta-oxidation defects.J Inherit Metab Dis 2001;24:337-344.
[34]Ohkuma A,Hayashi Y,Noguchi S,Nonaka I,Nishino I.Clinicopathological features of Japanese patients with PNPLA2 gene mutation.Neuromuscular Disorders 2007; 17:863-863.
[35] Horvath R, Schneiderat P, Schoser BGH, et al. Coenzyme Q10 deficiency and isolated myopathy. Neurology 2006; 66:253-255.
[36] Topaloglu H, Talim B, Orhan D, Haliloglu G, Horwath R, Kale G. Isolated myopathy with muscle coenzyme Q10 deficiency. Neuromuscular Disorders 2006; 16:659-659.
[37] Boitier E, Degoul F, Desguerre I, et al. A case of mitochondrial encephalomyopathy associated with a muscle coenzyme Q10 deficiency. J Neurol Sci 1998; 156:41-46.
[38] Fryburg JS, Pelegano JP, Bennett MJ, Bebin EM. Long-chain 3-hydroxyacyl-coenzyme A dehydrogenase (L-CHAD) deficiency in a patient with the Bannayan-Riley-Ruvalcaba syndrome. American journal of medical genetics 1994; 52:97-102.
[39] Antozzi C, Garavaglia B, Mora M, et al. Late-Onset Riboflavin-Responsive Myopathy with Combined Multiple Acyl-Coenzyme-a Dehydrogenase and Respiratory-Chain Deficiency. Neurology 1994; 44:2153-2158.
[40] Olsen RKJ, Andresen BS, Christensen E, Bross P, Skovby F, Gregersen N. Clear relationship between ETF/ETFDH genotype and phenotype in patients with multiple Acyl-CoA dehydrogenation deficiency. Human Mutation 2003; 22:12-23.
[41] Pramono Z, Lai P, Tan I, Lim M, Seah I, Yee W. Late onset multiple acyl-CoA dehydrogenase deficiency (MADD) associated with novel ETFDH mutations in two Chinese patients. Neuromuscular Disorders 2007; 17:864-864.
[42] Chiong MA, Sim KG, Carpenter K, et al. Transient multiple acyl-CoA dehydrogenation deficiency in a newborn female caused by maternal riboflavin deficiency. Molecular Genetics and Metabolism 2007; 92:109-114.
[43] Zhang J, Frerman FE, Kim JJ. Structure of electron transfer flavoprotein-ubiquinone oxidoreductase and electron transfer to the mitochondrial ubiquinone pool. Proceedings of the National Academy of Sciences of the United States of America 2006; 103:16212-16217.
[44] Robinson K, BD L. Covalent attachment of FAD to the yeast succinate dehydragenase flavoprotein requires import into mitochondria,presequence removal and folding. J Biol Chem 1996:4055-4060.
[45] Saijo T, Tanaka K. Isoalloxazine ring of FAD is required for the formation of the core in the Hsp60-assisted folding of medium chain acyl-CoA dehydrogenase subunit into the assembly competent conformation in mitochondria. J Biol Chem 1995; 270:1899-1907.
[46] Rhead W, Roettger V, Marshall T, Amendt B. Multiple Acyl-Coenzyme a Dehydrogenation Disorder Responsive to Riboflavin - Substrate Oxidation, Flavin Metabolism, and Flavoenzyme Activities in Fibroblasts. Pediatric Research 1993; 33:129-135.
[47] Bates C. Riboflavin. Int J Vitamine Nutr Res 1993:274-277.
[48] Nagao M, Tanaka K. FAD-dependent regulation of transcription, translation, post-translational processing, and post-processing stability of various mitochondrial acyl-CoA dehydrogenases and of electron transfer fiavoprotein and the site of holoenzyme formation. J Biol Chem 1992; 267:17925-17932.
[49] Hiltunen JK, Qin Y. beta-oxidation - strategies for the metabolism of a wide variety of acyl-CoA esters. Biochimica et biophysica acta 2000; 1484:117-128.
[2]Bradley WG,Hudgson P,Gardner-Medwin D,Walton JN.Myopathy associated with abnormal lipid metabolism in skeletal muscle.Lancet 1969;1:495-498.
[3]曹佩芝,吕丹云,夏谦,吴淑平.脂质沉积性肌病2例报告.中华神经精神科杂志 1990;4:216-218.
[4]李大年,刘淑萍,焉传祝,等.脂质沉积性肌病.临床神经病学杂志1995;8:73-75.
[5]王翠娣,殷剑,许贤豪,等.脂质沉积性肌病8例临床病理研究.中华病理学杂志2001;30:19-22.
[6]林红,王柠,慕容慎行,等.脂质沉积性肌病15例临床与病理分析.福建医科大学学报2000;34.
[7]狄晴,张平,张颖冬.脂质沉积性肌病临床及病理特点.临床神经病学杂志1998;11:280-282.
[8]姚璇,刘永海,许东升.脂质沉积性肌病6例临床分析.徐州医学院学报2000;20:163-164.
[9]吕海东,杨斌,秦东香,等.脂质沉积性肌病的临床与病理分析.实用神经疾病杂志2005;8:2-4.
[10]毕桂楠,梁莹,马朝桂.脂质沉积性肌病5例临床病理报道.广西医科大学学报1999;16:133.
[11]韩漫夫,赫秋月.肌活检诊断脂质沉积性肌病4例报道.中国实用内科杂志1999:19:632-633.
[12]Li W.,Yan C.Z.,Wu J.L.,et al.Therapeutic efects and long term follow-ups in 42case,s of ljpjd storage myopathy.Chin J Neur 2007;40:229-231.
[13]Gempel K,Topaloglu H,Talim B,et al.The myopathic form of coenzyme Q10deficiency is caused by mutations in the electron-transferring-flavoprotein dehydrogenase(ETFDH) gene.Brain 2007;130:2037-2044.
[14]Olsen RKJ,Pourfarzam M,Morris AAM,et al.Lipid-storage myopathy and respiratory insufficiency due to ETFQO mutations in a patient with late-onset multiple acyl-CoA dehydrogenation deficiency.Journal of Inherited Metabolic Disease 2004;27:671-678.
[15]Bressler R.Camitine and the twins.NEnglJMed 1970:745.
[16]Vielhaber S,Feistner H,Weis J,et al.Primary camitine deficiency:adult onset lipid storage myopathy with a mild clinical course.J Clin Neurosci 2004;11:919-924.
[17]Donato SD,Taroni F,editors,Myology,Basic and Clinical,the third edition,3 ed.New York:McGraw-Hill,2003.
[18]赵玉英,焉传祝.第62例-间歇性呕吐、进行性四肢无力.中华神经科杂志;41:61-63.
[19]Gordon N.Glutaric aciduria types Ⅰ and Ⅱ.Brain & Development 2006;28:136-140.
[20]杨艳玲,木村正彦,袁云,et al.戊二酸尿症Ⅱ型所致脂肪沉积性肌肉病的诊断与治疗分析.中华神经科杂志2004;5:438-441.
[21]梁雁,刘丽,魏虹,罗小平,王慕逖.维生素B2治疗有效的晚发型戊二酸尿症Ⅱ型.中华儿科杂志2003;12:916-920.
[22]Wanders RJ,Vreken P,den Boer ME,Wijburg FA,van Gennip AH,L IJ.Disorders of mitochondrial fatty acyl-CoA beta-oxidation.J Inherit Metab Dis 1999;22:442-487.
[23]Nezu J,Tamai I,Oku A,et al.Primary systemic camitine deficiency is caused by mutations in a gene encoding sodium ion-dependent camitine transporter.Nature genetics 1999;21:91-94.
[24]Iacobazzi V,Invemizzi F,Baratta S,et al.Molecular and functional analysis of SLC25A20 mutations causing carnitine-acylcamitine translocase deficiency.Hum Mutat 2004;24:312-320.
[25]Haap M,Thamer C,Machann J,et al.Metabolic characterization of a woman homozygous for the Ser113Leu missense mutation in carnitine palmitoyl transferase Ⅱ.The Journal of clinical endocrinology and metabolism 2002;87:2139-2143.
[26]李大年,现代神经内科学,1 ed.济南:山东科学技术出版社,2002.
[27]Angelini C,editor,Disorders of lipid metabolism,2007.
[28]Olsen RKJ,Olpin SE,Andresen BS,et al.ETFDH mutations as a major cause of riboflavin-responsive multiple acyl-CoA dehydrogenation deficiency.Brain 2007;130:2045-2054.
[29]Goodman SI,Binard RJ,Woontner MR,Frerman FE.Glutaricacidemia type Ⅱ:gene structure and mutations of the electron transfer flavoprotein:ubiquinone oxidoreductase(ETF:QO) gene.Molecular Genetics and Metabolism 2002:86-90.
[30]Tein I,Elpeleg O,Ben-Zeev B,et al.Short-chain acyl-CoA dehydrogenase gene mutation(c.319C ＞ T) presents with clinical heterogeneity and is candidate founder mutation in individuals of Ashkenazi Jewish origin.Molecular Genetics and Metabolism 2008;93:179-189.
[31]Tumbull DM,Bartlett K,Stevens DL,et al.Short-chain acyl-CoA dehydrogenase deficiency associated with a lipid-storage myopathy and secondary carnitine deficiency.The New England journal of medicine 1984;311:1232-1236.
[32]Aoyama T,Uchida Y,Kelley RI,et al.A novel disease with deficiency of mitochondrial very-long-chain acyl-CoA dehydrogenase.Biochem Biophys Res Commun 1993;191:1369-1372.
[33]Onkenhout W,Venizelos V,Scholte HR,De Klerk JB,Poorthuis BJ.Intermediates of unsaturated fatty acid oxidation are incorporated in triglycerides but not in phospholipids in tissues from patients with mitochondrial beta-oxidation defects.J Inherit Metab Dis 2001;24:337-344.
[34]Ohkuma A,Hayashi Y,Noguchi S,Nonaka I,Nishino I.Clinicopathological features of Japanese patients with PNPLA2 gene mutation.Neuromuscular Disorders 2007; 17:863-863.
[35] Horvath R, Schneiderat P, Schoser BGH, et al. Coenzyme Q10 deficiency and isolated myopathy. Neurology 2006; 66:253-255.
[36] Topaloglu H, Talim B, Orhan D, Haliloglu G, Horwath R, Kale G. Isolated myopathy with muscle coenzyme Q10 deficiency. Neuromuscular Disorders 2006; 16:659-659.
[37] Boitier E, Degoul F, Desguerre I, et al. A case of mitochondrial encephalomyopathy associated with a muscle coenzyme Q10 deficiency. J Neurol Sci 1998; 156:41-46.
[38] Fryburg JS, Pelegano JP, Bennett MJ, Bebin EM. Long-chain 3-hydroxyacyl-coenzyme A dehydrogenase (L-CHAD) deficiency in a patient with the Bannayan-Riley-Ruvalcaba syndrome. American journal of medical genetics 1994; 52:97-102.
[39] Antozzi C, Garavaglia B, Mora M, et al. Late-Onset Riboflavin-Responsive Myopathy with Combined Multiple Acyl-Coenzyme-a Dehydrogenase and Respiratory-Chain Deficiency. Neurology 1994; 44:2153-2158.
[40] Olsen RKJ, Andresen BS, Christensen E, Bross P, Skovby F, Gregersen N. Clear relationship between ETF/ETFDH genotype and phenotype in patients with multiple Acyl-CoA dehydrogenation deficiency. Human Mutation 2003; 22:12-23.
[41] Pramono Z, Lai P, Tan I, Lim M, Seah I, Yee W. Late onset multiple acyl-CoA dehydrogenase deficiency (MADD) associated with novel ETFDH mutations in two Chinese patients. Neuromuscular Disorders 2007; 17:864-864.
[42] Chiong MA, Sim KG, Carpenter K, et al. Transient multiple acyl-CoA dehydrogenation deficiency in a newborn female caused by maternal riboflavin deficiency. Molecular Genetics and Metabolism 2007; 92:109-114.
[43] Zhang J, Frerman FE, Kim JJ. Structure of electron transfer flavoprotein-ubiquinone oxidoreductase and electron transfer to the mitochondrial ubiquinone pool. Proceedings of the National Academy of Sciences of the United States of America 2006; 103:16212-16217.
[44] Robinson K, BD L. Covalent attachment of FAD to the yeast succinate dehydragenase flavoprotein requires import into mitochondria,presequence removal and folding. J Biol Chem 1996:4055-4060.
[45] Saijo T, Tanaka K. Isoalloxazine ring of FAD is required for the formation of the core in the Hsp60-assisted folding of medium chain acyl-CoA dehydrogenase subunit into the assembly competent conformation in mitochondria. J Biol Chem 1995; 270:1899-1907.
[46] Rhead W, Roettger V, Marshall T, Amendt B. Multiple Acyl-Coenzyme a Dehydrogenation Disorder Responsive to Riboflavin - Substrate Oxidation, Flavin Metabolism, and Flavoenzyme Activities in Fibroblasts. Pediatric Research 1993; 33:129-135.
[47] Bates C. Riboflavin. Int J Vitamine Nutr Res 1993:274-277.
[48] Nagao M, Tanaka K. FAD-dependent regulation of transcription, translation, post-translational processing, and post-processing stability of various mitochondrial acyl-CoA dehydrogenases and of electron transfer fiavoprotein and the site of holoenzyme formation. J Biol Chem 1992; 267:17925-17932.
[49] Hiltunen JK, Qin Y. beta-oxidation - strategies for the metabolism of a wide variety of acyl-CoA esters. Biochimica et biophysica acta 2000; 1484:117-128.