气相色谱质谱联用技术在新生儿遗传代谢病筛查中的应用
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摘要
遗传代谢病(IEM)是一组由于基因突变引起的疾病,一旦发病危害严重,因此世界上许多国家都已开展新生儿筛查项目。气相色谱质谱技术(GC-MS)具有高分离,高灵敏度、高特异性的定性定量特点,是一种筛查IEM的有力工具。GC-MS在筛查IEM方面已被应用多年,可以同时检测多种代谢疾病。本文将主要对气相色谱质谱技术的技术原理以及其在在新生儿遗传代谢病筛查中的优势特点、应用情况作一介绍。
Inborn errors of metabolism(IEM)are a group of metabolic disorders caused by genetic mutations and may lead to serious clinical consequences. Thus,newborn screening(NBS)has been performed in many countries to detect these disorders before they become symptomatic. Gas chromatography-mass spectrometry(GC-MS),due to its high chromatographic performance and highly sensitive and specific identification and quantification,has been proven to be an effective technology for NBS of IEM. This powerful technique enables accurate chemical diagnosis of various IEM and has been available for several decades. In this paper,the characteristics of GC-MS were introduced and its application in screening and monitoring IEM were summarized.
Inborn errors of metabolism(IEM)are a group of metabolic disorders caused by genetic mutations and may lead to serious clinical consequences. Thus,newborn screening(NBS)has been performed in many countries to detect these disorders before they become symptomatic. Gas chromatography-mass spectrometry(GC-MS),due to its high chromatographic performance and highly sensitive and specific identification and quantification,has been proven to be an effective technology for NBS of IEM. This powerful technique enables accurate chemical diagnosis of various IEM and has been available for several decades. In this paper,the characteristics of GC-MS were introduced and its application in screening and monitoring IEM were summarized.
引文
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[2]Arélin M,Beblo S.Newborn screening of metabolic disorders[J].Journal of Pediatric Endocrinology&Metabolism Jpem,2016,29(1):1-3.
[3]Kamboj M.Clinical approach to the diagnoses of inborn errors of metabolism.[J].Pediatric Clinics of North America,2008,55(5):1113-1127.
[4]金力超,范玉明,侯晓蓉,等.色谱联用技术在药物分析中的应用特点和新趋势[J].药物分析杂志,2015(9):1520-1527.
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[13]Kuhara T.Diagnosis and monitoring of inborn errors of metabolism using f urease-pretreatment of urine,isotope dilution,and gas chromatography-mass spectrometry[J].Journal of Chromatography B:Biomedical Sciences and Applications,2002,781(1):497-517.
[14]罗小平,王慕逖,魏虹,等.尿滤纸片法气相色谱-质谱分析技术在遗传性代谢病高危筛查诊断中的应用[J].中华儿科杂志,2003,41(4):245-248.
[15]江敏妍,刘丽,李秀珍,等.尿GC-MS分析技术在遗传代谢缺陷病筛查诊断中的局限性[J].广东医学,2012,33(20):3062-3066.
[16]Jiang M,Liu L,Mei H,et al.Detection of inborn errors of metabolism using GC-MS:over 3 years of experience in southern China[J].J Pediatr Endocrinol Metab,2015,28(3-4):375-380.
[17]高平明,郝虎,李思涛,等.尿素酶预处理-气相色谱-质谱技术筛查遗传性代谢病高危儿[J].中华实用儿科临床杂志,2015,30(21):1569-1571.
[18]张万巧,彭薇,杨尧,等.气相色谱质谱法筛查先天性代谢缺陷方法及诊断标准的建立[J].中华实用诊断与治疗杂志,2015,29(11):1059-1062.
[19]Briand G,Lemaireewing S,Parente F,et al.Mass spectrometry and inherited metabolic diseases diagnosis[J].Ann Biol Clin,2015,73(1):93-106.
[20]Waterham H R,Koster J,Romeijn G J,et al.Mutations in the 3beta-hydroxysterol Delta24-reductase gene cause desmosterolosis,an autosomal recessive disorder of cholesterol biosynthesis[J].American Journal of Human Genetics,2001,69(4):685-694.
[21]Brunettipierri N,Corso G,Rossi M,et al.Lathosterolosis,a Novel Multiple-Malformation/Mental Retardation Syndrome Due to Deficiency of 3β-Hydroxysteroid-Δ5-Desaturase[J].American Journal of Human Genetics,2002,71(4):952-958.
[22]Herman G E,Kratz L.Disorders of sterol synthesis:Beyond Smith-Lemli-Opitz syndrome[J].American Journal of Medical Genetics Part C Seminars in Medical Genetics,2012,160C(4):301-321.
[23]Shackleton C H.Profiling steroid hormones and urinary steroids[J].J Chromatogr,1986,379(379):91-156.
[24]Ma?unowicz E M,Mitkowska Z,Bal K,et al.Definitive diagnosis of enzymatic deficiencies of steroidogenesis in at-risk newborns and infants by urinary marker analysis using GC/MS-SIM[J].Hormone Research in Paediatrics,1997,48(6):243-251.
[25]Caulfield M P,Lynn T,Gottschalk M E,et al.The diagnosis of congenital adrenal hyperplasia in the newborn by gas chromatography/mass spectrometry analysis of random urine specimens.[J].Journal of Clinical Endocrinology&Metabolism,2002,87(8):3682.
[26]Homma K,Hasegawa T,Masumoto M,et al.Reference values for urinary steroids in Japanese newborn infants:gas chromatography/mass spectrometry in selected ion monitoring.[J].Endocrine Journal,2003,50(6):783.
[27]丁一峰,顾学范,叶军,等.气相色谱-质谱分析新生儿尿液中类固醇激素方法的建立[J].临床儿科杂志,2010,28(8):748-751.
[28]辛颖.X-连锁肾上腺脑白质营养不良诊治[J].中国实用儿科杂志,2016,31(6):429-33.
[29]Moser A B,Kreiter N,Bezman L,et al.Plasma very long chain fatty acids in 3,000 peroxisome disease patients and 29,000controls[J].Annals of Neurology,1999,45(1):100.
[30]Suzuki Y,Shimozawa N,Yajima S,et al.Incidence of peroxisomal disorders in Japan[J].Japanese Journal of Human Genetics,1996,41(1):167-175.
[31]Unterberger U,Regelsberger G,Sundt R,et al.Diagnosis of X-linked adrenoleukodystrophy in blood leukocytes[J].Clinical Biochemistry,2007,40(13):1037-1044.
[32]Moser A,Jones R,Hubbard W,et al.Newborn Screening for X-Linked Adrenoleukodystrophy[J].International Journal of Neonatal Screening,2016,2(4):15.
[2]Arélin M,Beblo S.Newborn screening of metabolic disorders[J].Journal of Pediatric Endocrinology&Metabolism Jpem,2016,29(1):1-3.
[3]Kamboj M.Clinical approach to the diagnoses of inborn errors of metabolism.[J].Pediatric Clinics of North America,2008,55(5):1113-1127.
[4]金力超,范玉明,侯晓蓉,等.色谱联用技术在药物分析中的应用特点和新趋势[J].药物分析杂志,2015(9):1520-1527.
[5]Niessen WMA,Vandergreef J.Liquid chromatography--mass spectrometry:principles and applications[M].M.Dekker,1992,703(1-2):37-57.
[6]Rohloff J.Analysis of Phenolic and Cyclic Compounds in Plants Using Derivatization Techniques in Combination with GC-MS-Based Metabolite Profiling[J].Molecules,2015,20(2):3431-3462.
[7]Villani G R,Gallo G,Scolamiero E,et al."Classical organic acidurias":diagnosis and pathogenesis[J].Clinical&Experimental Medicine,2016:1-19.
[8]Budd M A,Tanaka K,Holmes L B,et al.Isovaleric acidemia.Clinical features of a new genetic defect of leucine metabolism.[J].N Engl J Med,1967,277(7):321-327.
[9]Shoemaker J D,Elliott W H.Automated screening of urine samples for carbohydrates,organic and amino acids after treatment with urease[J].J Chromatogr,1991,562(1-2):125-138.
[10]Kuhara T,Shinka T,Inoue Y,et al.Pilot study of gas chromatographic-mass spectrometric screening of newborn urine for inborn errors of metabolism after treatment with urease[J].Journal of Chromatography B Biomedical Sciences&Applications,1999,731(1):141.
[11]Matsumoto I,Kuhara T.A new chemical diagnostic method for inborn errors of metabolism by mass spectrometry-rapid,practical,and simultaneous urinary metabolites analysis[J].Mass Spectrometry Reviews,1996,15(1):43-57.
[12]Kuhara T.Diagnosis of inborn errors of metabolism using filter paper urine,urease treatment,isotope dilution and gas chromatography-mass spectrometry[J].Journal of Chromatography B:Biomedical Sciences and Applications,2001,758(1):3-25.
[13]Kuhara T.Diagnosis and monitoring of inborn errors of metabolism using f urease-pretreatment of urine,isotope dilution,and gas chromatography-mass spectrometry[J].Journal of Chromatography B:Biomedical Sciences and Applications,2002,781(1):497-517.
[14]罗小平,王慕逖,魏虹,等.尿滤纸片法气相色谱-质谱分析技术在遗传性代谢病高危筛查诊断中的应用[J].中华儿科杂志,2003,41(4):245-248.
[15]江敏妍,刘丽,李秀珍,等.尿GC-MS分析技术在遗传代谢缺陷病筛查诊断中的局限性[J].广东医学,2012,33(20):3062-3066.
[16]Jiang M,Liu L,Mei H,et al.Detection of inborn errors of metabolism using GC-MS:over 3 years of experience in southern China[J].J Pediatr Endocrinol Metab,2015,28(3-4):375-380.
[17]高平明,郝虎,李思涛,等.尿素酶预处理-气相色谱-质谱技术筛查遗传性代谢病高危儿[J].中华实用儿科临床杂志,2015,30(21):1569-1571.
[18]张万巧,彭薇,杨尧,等.气相色谱质谱法筛查先天性代谢缺陷方法及诊断标准的建立[J].中华实用诊断与治疗杂志,2015,29(11):1059-1062.
[19]Briand G,Lemaireewing S,Parente F,et al.Mass spectrometry and inherited metabolic diseases diagnosis[J].Ann Biol Clin,2015,73(1):93-106.
[20]Waterham H R,Koster J,Romeijn G J,et al.Mutations in the 3beta-hydroxysterol Delta24-reductase gene cause desmosterolosis,an autosomal recessive disorder of cholesterol biosynthesis[J].American Journal of Human Genetics,2001,69(4):685-694.
[21]Brunettipierri N,Corso G,Rossi M,et al.Lathosterolosis,a Novel Multiple-Malformation/Mental Retardation Syndrome Due to Deficiency of 3β-Hydroxysteroid-Δ5-Desaturase[J].American Journal of Human Genetics,2002,71(4):952-958.
[22]Herman G E,Kratz L.Disorders of sterol synthesis:Beyond Smith-Lemli-Opitz syndrome[J].American Journal of Medical Genetics Part C Seminars in Medical Genetics,2012,160C(4):301-321.
[23]Shackleton C H.Profiling steroid hormones and urinary steroids[J].J Chromatogr,1986,379(379):91-156.
[24]Ma?unowicz E M,Mitkowska Z,Bal K,et al.Definitive diagnosis of enzymatic deficiencies of steroidogenesis in at-risk newborns and infants by urinary marker analysis using GC/MS-SIM[J].Hormone Research in Paediatrics,1997,48(6):243-251.
[25]Caulfield M P,Lynn T,Gottschalk M E,et al.The diagnosis of congenital adrenal hyperplasia in the newborn by gas chromatography/mass spectrometry analysis of random urine specimens.[J].Journal of Clinical Endocrinology&Metabolism,2002,87(8):3682.
[26]Homma K,Hasegawa T,Masumoto M,et al.Reference values for urinary steroids in Japanese newborn infants:gas chromatography/mass spectrometry in selected ion monitoring.[J].Endocrine Journal,2003,50(6):783.
[27]丁一峰,顾学范,叶军,等.气相色谱-质谱分析新生儿尿液中类固醇激素方法的建立[J].临床儿科杂志,2010,28(8):748-751.
[28]辛颖.X-连锁肾上腺脑白质营养不良诊治[J].中国实用儿科杂志,2016,31(6):429-33.
[29]Moser A B,Kreiter N,Bezman L,et al.Plasma very long chain fatty acids in 3,000 peroxisome disease patients and 29,000controls[J].Annals of Neurology,1999,45(1):100.
[30]Suzuki Y,Shimozawa N,Yajima S,et al.Incidence of peroxisomal disorders in Japan[J].Japanese Journal of Human Genetics,1996,41(1):167-175.
[31]Unterberger U,Regelsberger G,Sundt R,et al.Diagnosis of X-linked adrenoleukodystrophy in blood leukocytes[J].Clinical Biochemistry,2007,40(13):1037-1044.
[32]Moser A,Jones R,Hubbard W,et al.Newborn Screening for X-Linked Adrenoleukodystrophy[J].International Journal of Neonatal Screening,2016,2(4):15.