重视脂肪酸氧化代谢病的筛查与诊治
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摘要
脂肪酸氧化代谢病(fatty acid oxidation disorders,FAOD)是脂肪酸氧化代谢过程中十余种疾病的总称,均属于常染色体隐性遗传病,是常见的遗传代谢病,从新生儿至成人均可发病,临床表现无特异性,主要表现为肝病、心肌病及肌肉疾病。串联质谱检测血游离肉碱、酰基肉碱水平及基因检测是诊断此类疾病的重要方法。串联质谱新生儿筛查有助于FAOD的早诊断及早治疗。原发性肉碱缺乏症及多种酰基辅酶A脱氢酶缺乏症有特异治疗药物,效果较好,其他疾病无特异药物,需要对症治疗。
Fatty acid oxidation disorders(FAOD)include more than 10 kinds of diseases,they all belong to autosomal recessive diseases and are common inherited metabolic diseases. Onset age of the patients with FAOD are from newborn to adult. The clinical manifestations were nonspecific,mainly manifested as liver disease,cardiomyopathy and muscle diseases. Detection of free carnitine and acylcarnitines in blood by tandem mass spectrometry and detection of gene mutations are important methods for diagnosis of such diseases. Tandem mass screening for neonatal screening is helpful for early diagnosis and early treatment of FAOD. Primary carnitine deficiency and multiple acyl-CoA dehydrogenase deficiency can be treated by specific therapeutic drugs with good effect. There are no specific drugs for other diseases,which need symptomatic treatment.
Fatty acid oxidation disorders(FAOD)include more than 10 kinds of diseases,they all belong to autosomal recessive diseases and are common inherited metabolic diseases. Onset age of the patients with FAOD are from newborn to adult. The clinical manifestations were nonspecific,mainly manifested as liver disease,cardiomyopathy and muscle diseases. Detection of free carnitine and acylcarnitines in blood by tandem mass spectrometry and detection of gene mutations are important methods for diagnosis of such diseases. Tandem mass screening for neonatal screening is helpful for early diagnosis and early treatment of FAOD. Primary carnitine deficiency and multiple acyl-CoA dehydrogenase deficiency can be treated by specific therapeutic drugs with good effect. There are no specific drugs for other diseases,which need symptomatic treatment.
引文
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[3]Vitoria I,Martín-Hernández E,Pe?a-Quintana L,et al.Carnitine-acylcarnitine translocase deficiency:experience with four cases in Spain and review of the literature[J].JIMD Rep,2014:11-18.
[4]Merritt JL 2nd,Vedal S,Abdenur JE,et al.Infants suspected to have very-long chain acyl-CoA dehydrogenase deficiency from newborn screening[J].Mol Genet Metab,2014,111(4):484-492.
[5]Magoulas PL.Systemic primary carnitine deficiency:an overview of clinical manifestations,diagnosis,and management[J].Orphanet J Rare Dis,2012,7(1):68.
[6]Béhin A,Acquaviva-Bourdain C,Souvannanorath S,et al.Multiple acyl-CoA dehydrogenase deficiency(MADD)as a cause of late-onset treatable metabolic disease[J].Rev Neurol(Paris),2016,172(3):231-241.
[7]韩连书,叶军,邱文娟,等.原发性肉碱缺乏症17例诊治与随访[J].中华儿科杂志,2012,50(6):405-409.
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[9]Han L,Han F,Ye J,et al.Spectrum analysis of common inherited metabolic diseases in Chinese patients screened and diagnosed by tandem mass spectrometry[J].J Clin Lab Anal,2015,29(2):162-168.
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[13]韩连书.遗传代谢病检测技术的应用及其结果的临床判读[J].中国实用儿科杂志,2014,29(8):569-574.
[14]Xi J,Wen B,Lin J,et al.Clinical features and ETFDH mutation spectrum in a cohort of 90 Chinese patients with late-onset multiple acyl-CoA dehydrogenase deficiency[J].J Inherit Metab Dis,2014,37(3):399-404.
[15]Henriques BJ,Bross P,Gomes CM.Mutational hotspots in electron transfer flavoprotein underlie defective folding and function in multiple acyl-CoA dehydrogenase deficiency[J].Biochim Biophys Acta,2010,1802(11):1070-1077.
[16]Liang WC,Ohkuma A,Hayashi YK,et al.ETFDH mutations,CoQ10 levels,and respiratory chain activities in patients with riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency[J].Neuromuscular Disord,2009,19(3):212-216.
[17]Wilcken B,Wiley V,Hammond J,et al.Screening newborns for inborn errors of metabolism by tandem mass spectrometry[J].N Engl J Med,2003,348(23):2304-2312.
[18]Spiekerkoetter U.Mitochondrial fatty acid oxidation disorders:clinical presentation of long-chain fatty acid oxidation defects before and after newborn screening[J].J Inherit Metab Dis,2010,33(5):527-532.
[19]Lee NC,Tang NL,Chien YH,et al.Diagnoses of newborns and mothers with carnitine uptake defects through newborn screening[J].Mol Genet Metab,2010,100(1):46-50.
[20]Holm IA,Agrawal PB,Ceyhan-Birsoy O,et al.The BabySeq project:implementing genomic sequencing in newborns[J].BMCPediatr,2018,18(1):225.
[21]King JS,Smith ME.Whole-genome screening of newborns?The constitutional boundaries of state newborn screening programs[J].Pediatrics,2016,137(Suppl 1):S8-15.
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[23]Howard HC,Knoppers BM,Cornel MC,et al.Whole-genome sequencing in newborn screening?A statement on the continued importance of targeted approaches in newborn screening programmes[J].Eur J Hum Genet,2015,23(12):1593-1600.
[24]Yamada K,Taketani T.Management and diagnosis of mitochondrial fatty acid oxidation disorders:focus on very-longchain acyl-CoA dehydrogenase deficiency[J].J Hum Genet,2018.[Epub ahead of print]
[25]Frazier DM,Millington DS,Mccandless SE,et al.The tandem mass spectrometry newborn screening experience in North Carolina:1997-2005[J].J Inherit Metab Dis,2006,29(1):76-85.
[26]Potter BK,Little J,Chakraborty P,et al.Variability in the clinical management of fatty acid oxidation disorders:results of a survey of Canadian metabolic physicians[J].J Inherit Metab Dis,2012,35(1):115-123.
[2]Gregersen N,Andresen BS,Pedersen CB,et al.Mitochondrial fatty acid oxidation defects-remaining challenges[J].J Inherit Metab Dis,2008,31(5):643-657.
[3]Vitoria I,Martín-Hernández E,Pe?a-Quintana L,et al.Carnitine-acylcarnitine translocase deficiency:experience with four cases in Spain and review of the literature[J].JIMD Rep,2014:11-18.
[4]Merritt JL 2nd,Vedal S,Abdenur JE,et al.Infants suspected to have very-long chain acyl-CoA dehydrogenase deficiency from newborn screening[J].Mol Genet Metab,2014,111(4):484-492.
[5]Magoulas PL.Systemic primary carnitine deficiency:an overview of clinical manifestations,diagnosis,and management[J].Orphanet J Rare Dis,2012,7(1):68.
[6]Béhin A,Acquaviva-Bourdain C,Souvannanorath S,et al.Multiple acyl-CoA dehydrogenase deficiency(MADD)as a cause of late-onset treatable metabolic disease[J].Rev Neurol(Paris),2016,172(3):231-241.
[7]韩连书,叶军,邱文娟,等.原发性肉碱缺乏症17例诊治与随访[J].中华儿科杂志,2012,50(6):405-409.
[8]Gallant NM,Leydiker K,Tang H,et al.Biochemical,molecular,and clinical characteristics of children with short chain acyl-CoA dehydrogenase deficiency detected by newborn screening in California[J].Mol Genet Metab,2012,106(1):55-61.
[9]Han L,Han F,Ye J,et al.Spectrum analysis of common inherited metabolic diseases in Chinese patients screened and diagnosed by tandem mass spectrometry[J].J Clin Lab Anal,2015,29(2):162-168.
[10]郑静,张玉,洪芳,等.浙江省新生儿脂肪酸氧化代谢疾病筛查及随访分析[J].浙江大学学报(医学版),2017,46(3):248-255.
[11]Lindner M,Hoffmann GF,Matern D.Newborn screening for disorders of fatty-acid oxidation:experience and recommendations from an expert meeting[J].J Inherit Metab Dis,2010,33(5):521-526.
[12]Kang E,Kim YM,Kang M,et al.Clinical and genetic characteristics of patients with fatty acid oxidation disorders identified by newborn screening[J].Bmc Pediatrics,2018,18(1):103.
[13]韩连书.遗传代谢病检测技术的应用及其结果的临床判读[J].中国实用儿科杂志,2014,29(8):569-574.
[14]Xi J,Wen B,Lin J,et al.Clinical features and ETFDH mutation spectrum in a cohort of 90 Chinese patients with late-onset multiple acyl-CoA dehydrogenase deficiency[J].J Inherit Metab Dis,2014,37(3):399-404.
[15]Henriques BJ,Bross P,Gomes CM.Mutational hotspots in electron transfer flavoprotein underlie defective folding and function in multiple acyl-CoA dehydrogenase deficiency[J].Biochim Biophys Acta,2010,1802(11):1070-1077.
[16]Liang WC,Ohkuma A,Hayashi YK,et al.ETFDH mutations,CoQ10 levels,and respiratory chain activities in patients with riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency[J].Neuromuscular Disord,2009,19(3):212-216.
[17]Wilcken B,Wiley V,Hammond J,et al.Screening newborns for inborn errors of metabolism by tandem mass spectrometry[J].N Engl J Med,2003,348(23):2304-2312.
[18]Spiekerkoetter U.Mitochondrial fatty acid oxidation disorders:clinical presentation of long-chain fatty acid oxidation defects before and after newborn screening[J].J Inherit Metab Dis,2010,33(5):527-532.
[19]Lee NC,Tang NL,Chien YH,et al.Diagnoses of newborns and mothers with carnitine uptake defects through newborn screening[J].Mol Genet Metab,2010,100(1):46-50.
[20]Holm IA,Agrawal PB,Ceyhan-Birsoy O,et al.The BabySeq project:implementing genomic sequencing in newborns[J].BMCPediatr,2018,18(1):225.
[21]King JS,Smith ME.Whole-genome screening of newborns?The constitutional boundaries of state newborn screening programs[J].Pediatrics,2016,137(Suppl 1):S8-15.
[22]Kingsmore SF.Newborn testing and screening by whole-genome sequencing[J].Genet Med,2016,18(3):214-216.
[23]Howard HC,Knoppers BM,Cornel MC,et al.Whole-genome sequencing in newborn screening?A statement on the continued importance of targeted approaches in newborn screening programmes[J].Eur J Hum Genet,2015,23(12):1593-1600.
[24]Yamada K,Taketani T.Management and diagnosis of mitochondrial fatty acid oxidation disorders:focus on very-longchain acyl-CoA dehydrogenase deficiency[J].J Hum Genet,2018.[Epub ahead of print]
[25]Frazier DM,Millington DS,Mccandless SE,et al.The tandem mass spectrometry newborn screening experience in North Carolina:1997-2005[J].J Inherit Metab Dis,2006,29(1):76-85.
[26]Potter BK,Little J,Chakraborty P,et al.Variability in the clinical management of fatty acid oxidation disorders:results of a survey of Canadian metabolic physicians[J].J Inherit Metab Dis,2012,35(1):115-123.