两种质谱技术在小儿重症遗传代谢病诊断的应用及评价
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摘要
目的探讨小儿重症监护病房遗传代谢病的发生率,评价气相色谱-质谱(GC-MS)和串联质谱技术(MSMS)对遗传代谢性疾病的应用价值。方法选取2015年1月-2018年10月我院收治的重症遗传代谢性疾病患儿43例,采用GCMS、MS-MS技术进行诊断,分析患儿主要临床症状表现以及预后。我们将所有病例进行两种方式进行检测。结果 43例代谢性疾病患儿临床表现为反复代谢性酸中毒,意识障碍,严重电解质紊乱,不明原因肝功能障碍,黄疸,凝血功能障碍,血氨增高等主要症状;发现用GC-MS检测尿标本阳性24例,阳性率为55.81%,用MS-MS检测血标本检测出阳性30例,阳性率为69.77%。结合基因等实验室方法检查结果最终确诊为:甲基丙二酸血症9例,原发性肉碱缺乏症4例,希特林蛋白缺乏症2例,β酮硫解酶缺乏4例,线粒体疾病3例,尼曼匹克病3例,高苯丙酸血症2例,糖原累积病2例,多种酰基辅酶A脱氢酶缺乏症2例,生物素酶缺乏症2例,鸟氨酸氨甲酰基转移酶缺乏症2例,酪氨酸血症2例,枫糖血症1例,戊二酸血症1例,异戊酸血症1例,极长链酰辅酶A脱氢酶缺乏症1例,肉碱棕榈酰转移酶缺乏症1例,粘多糖贮积症1例,肝豆状核变性1例。以上疾病症状都较为隐匿,不易发现,在临床诊治中容易出现误诊、漏诊。结论小儿重症监护病房遗传代谢病临床分析过程中,患儿主要表现为发育落后,喂养困难,意识障碍,惊厥,严重代酸等。对患儿尽早进行血、尿标本遗传代谢病筛查,两种方法不能互为代替。但部分疾病的确诊往往要结合基因检查等实验室检查结果进行综合分析才能做出,及时合理治疗能挽救更多危重患儿并改善预后。
Objective:To investigate the incidence of genetic metabolic diseases in pediatric intensive care unit(ICU),and to evaluate the application value of gas chromatography-mass spectrometry(GC-MS)and tandem mass spectrometry(MS-MS)in genetic metabolic diseases. Methods:43 children with severe genetic and metabolic diseases were selected from January 2015 to October 2018 in our hospital. The main clinical symptoms and prognosis were analyzed by using GC-MS and MS-MS techniques.Results:The clinical manifestations of 43 children with metabolic diseases were malnutrition,metabolic acidosis,disturbance of consciousness,vomiting and other major symptoms. It was found that 24 urine samples were positive by GC-MS,the positive rate was 55.81%,and 30 blood samples were positive by MS-MS,the positive rate was 69.77%. The results of combined gene and other laboratory methods were as follows:methylmalonic acidemia in 9 cases,primary carnitine deficiency in 4 cases,hitlen protein deficiency in 2 cases,beta ketothiolylase deficiency in 4 cases,mitochondrial disease in 3 cases,Niemannipik disease in 3 cases,hyperphenylpropionemia in 2 cases,glycogen accumulation disease in 2 cases,multiple acyl coenzyme A dehydrogenase deficiency in 2 cases. There were 2 cases of biotin deficiency,2 cases of ornithine carbamyltransferase deficiency,2 cases of tyrosinemia,1 case of maple glycemia,1 case of glutaric acidemia,1 case of isovaleridemia,1 case of very long chain acyl coenzyme A dehydrogenase deficiency,1 case of carnitine palmitoyltransferase deficiency,1 case of mucopolysaccharide storage and 1 case of hepatolenticular degeneration. All of the above symptoms are hidden and difficult to detect. They are prone to misdiagnosis and missed diagnosis in clinical diagnosis and treatment. ConclusionIn:The clinical analysis of hereditary metabolic diseases in children's intensive care unit,the main manifestations of these diseases are backward development,difficulty in feeding,disturbance of consciousness,convulsions,severe acid substitution,etc. As for early screening of blood and urine specimens for genetic metabolic diseases,the two methods can not be substituted for each other. However,the diagnosis of some diseases often needs to be combined with the results of laboratory tests such as genetic tests to make a comprehensive analysis,timely and reasonable treatment can save more critically ill children and improve the prognosis.
Objective:To investigate the incidence of genetic metabolic diseases in pediatric intensive care unit(ICU),and to evaluate the application value of gas chromatography-mass spectrometry(GC-MS)and tandem mass spectrometry(MS-MS)in genetic metabolic diseases. Methods:43 children with severe genetic and metabolic diseases were selected from January 2015 to October 2018 in our hospital. The main clinical symptoms and prognosis were analyzed by using GC-MS and MS-MS techniques.Results:The clinical manifestations of 43 children with metabolic diseases were malnutrition,metabolic acidosis,disturbance of consciousness,vomiting and other major symptoms. It was found that 24 urine samples were positive by GC-MS,the positive rate was 55.81%,and 30 blood samples were positive by MS-MS,the positive rate was 69.77%. The results of combined gene and other laboratory methods were as follows:methylmalonic acidemia in 9 cases,primary carnitine deficiency in 4 cases,hitlen protein deficiency in 2 cases,beta ketothiolylase deficiency in 4 cases,mitochondrial disease in 3 cases,Niemannipik disease in 3 cases,hyperphenylpropionemia in 2 cases,glycogen accumulation disease in 2 cases,multiple acyl coenzyme A dehydrogenase deficiency in 2 cases. There were 2 cases of biotin deficiency,2 cases of ornithine carbamyltransferase deficiency,2 cases of tyrosinemia,1 case of maple glycemia,1 case of glutaric acidemia,1 case of isovaleridemia,1 case of very long chain acyl coenzyme A dehydrogenase deficiency,1 case of carnitine palmitoyltransferase deficiency,1 case of mucopolysaccharide storage and 1 case of hepatolenticular degeneration. All of the above symptoms are hidden and difficult to detect. They are prone to misdiagnosis and missed diagnosis in clinical diagnosis and treatment. ConclusionIn:The clinical analysis of hereditary metabolic diseases in children's intensive care unit,the main manifestations of these diseases are backward development,difficulty in feeding,disturbance of consciousness,convulsions,severe acid substitution,etc. As for early screening of blood and urine specimens for genetic metabolic diseases,the two methods can not be substituted for each other. However,the diagnosis of some diseases often needs to be combined with the results of laboratory tests such as genetic tests to make a comprehensive analysis,timely and reasonable treatment can save more critically ill children and improve the prognosis.
引文
[1]石惠英,杨长仪,张宝泉,等.新生儿重症监护病房遗传代谢病临床分析[J].中华实用儿科临床杂志,2016,31(20):1556-1558.
[2]曾伟宏,欧阳海梅,梁嘉颖,等.气相色谱-质谱联用技术在遗传代谢病诊断和治疗监测中的应用[J].广东医学,2017,38(19):2997-3000.
[3]Hoofnagle A N,Laha T J,Rainey P M,et al. Specific Detection of Anabasine,Nicotine,and Nicotine Metabolites in Urine by Liquid Chromatography-Tandem Mass Spectrometry[J]. American Journal of Clinical Pathology,2016,126(6):880-887.
[4]王少亭,李艳.液相色谱-质谱联用技术在临床检验中的应用与发展[J].中华检验医学杂志,2016,39(8):650-653.
[5]杨宇奇,蒋曙红,韩小亚,等.20027例新生儿遗传代谢病串联质谱筛查的初步报告[J].重庆医学,2018,9(2):246-249.
[6]WooHI,YangJS,OhHJ,etal.Asimpleandrapid analytical method based on solid-phase extraction and liquid chromatography-tandem mass spectrometry for the simultaneous determination of free catecholamines and metanephrines in urine and its application to routine clinical analysis[J]. Clinical Biochemistry,2016,49(7-8):573-579.
[7]尚世强,杨建滨,王治国.新生儿遗传代谢病串联质谱筛查存在的问题及展望[J].中华检验医学杂志,2016,39(4):237-239.
[8]马艳华,闫宽,董颖.用液相色谱-串联质谱技术研究禁用物质氢氯噻嗪在人尿中的代谢情况[J].中国运动医学杂志,2016,35(1):67-70.
[9]Ko J M,Park K S,Kang Y,et al. A New Integrated Newborn Screening Workflow Can Provide a Shortcut to Differential Diagnosis and Confirmation of Inherited Metabolic Diseases.[J].Yonsei Medical Journal,2018,59(5):652-661.
[10]林书祥,舒剑波,王朝,等.15851例遗传代谢病高危患儿的临床分析[J].中国当代儿科杂志,2017,19(12):1243-1247.
[11]陈世范,杨静波,张敏,等.超滤法结合纳升液相色谱-串联质谱技术分析漏出性胸腔积液中多肽组分[J].分析化学,2017,45(2):224-230.
[12] Mütze U. Jean-Marie Saudubray,Matthias R. Baumgartner,John Walter(Eds.). Inborn metabolic diseases:diagnosis and treatment:2016,658 pp(ISBN 978-3-66249771-5)[J]. Journal of Inherited Metabolic Disease,2016,40(1):1-1.
[13]陈乡,刘露,周文浩.遗传代谢性疾病相关孤儿药研究进展[J].国际药学研究杂志,2017,44(2):167-172.
[14]谭跃球.遗传代谢病的生殖干预[J].中华实用儿科临床杂志,2017,32(8):565-569.
[15] Kremer L S,Stead C L,Lesimple P,et al. Severe respiratory complex III defect prevents liver adaptation to prolonged fasting[J].Journal of Hepatology,2016,65(2):377-385.
[2]曾伟宏,欧阳海梅,梁嘉颖,等.气相色谱-质谱联用技术在遗传代谢病诊断和治疗监测中的应用[J].广东医学,2017,38(19):2997-3000.
[3]Hoofnagle A N,Laha T J,Rainey P M,et al. Specific Detection of Anabasine,Nicotine,and Nicotine Metabolites in Urine by Liquid Chromatography-Tandem Mass Spectrometry[J]. American Journal of Clinical Pathology,2016,126(6):880-887.
[4]王少亭,李艳.液相色谱-质谱联用技术在临床检验中的应用与发展[J].中华检验医学杂志,2016,39(8):650-653.
[5]杨宇奇,蒋曙红,韩小亚,等.20027例新生儿遗传代谢病串联质谱筛查的初步报告[J].重庆医学,2018,9(2):246-249.
[6]WooHI,YangJS,OhHJ,etal.Asimpleandrapid analytical method based on solid-phase extraction and liquid chromatography-tandem mass spectrometry for the simultaneous determination of free catecholamines and metanephrines in urine and its application to routine clinical analysis[J]. Clinical Biochemistry,2016,49(7-8):573-579.
[7]尚世强,杨建滨,王治国.新生儿遗传代谢病串联质谱筛查存在的问题及展望[J].中华检验医学杂志,2016,39(4):237-239.
[8]马艳华,闫宽,董颖.用液相色谱-串联质谱技术研究禁用物质氢氯噻嗪在人尿中的代谢情况[J].中国运动医学杂志,2016,35(1):67-70.
[9]Ko J M,Park K S,Kang Y,et al. A New Integrated Newborn Screening Workflow Can Provide a Shortcut to Differential Diagnosis and Confirmation of Inherited Metabolic Diseases.[J].Yonsei Medical Journal,2018,59(5):652-661.
[10]林书祥,舒剑波,王朝,等.15851例遗传代谢病高危患儿的临床分析[J].中国当代儿科杂志,2017,19(12):1243-1247.
[11]陈世范,杨静波,张敏,等.超滤法结合纳升液相色谱-串联质谱技术分析漏出性胸腔积液中多肽组分[J].分析化学,2017,45(2):224-230.
[12] Mütze U. Jean-Marie Saudubray,Matthias R. Baumgartner,John Walter(Eds.). Inborn metabolic diseases:diagnosis and treatment:2016,658 pp(ISBN 978-3-66249771-5)[J]. Journal of Inherited Metabolic Disease,2016,40(1):1-1.
[13]陈乡,刘露,周文浩.遗传代谢性疾病相关孤儿药研究进展[J].国际药学研究杂志,2017,44(2):167-172.
[14]谭跃球.遗传代谢病的生殖干预[J].中华实用儿科临床杂志,2017,32(8):565-569.
[15] Kremer L S,Stead C L,Lesimple P,et al. Severe respiratory complex III defect prevents liver adaptation to prolonged fasting[J].Journal of Hepatology,2016,65(2):377-385.