56例甲基丙二酸血症患儿的临床和串联质谱及气相色谱数据分析

Data analysis of tandem mass spectrometer and gas chromatography mass spectrometry in 56 cases of clinical infants with methylmalonic acidemia(MMA)

目的探讨56例甲基丙二酸血症的临床和串联质谱及气相色谱检测数据特征,为诊断MMA数据分析积累经验。方法汇总整理2013年1-12月份的56例（男27例,女29例）临床患儿的血串联质谱（游离肉碱（CO）、丙酰基肉毒碱（C3）、丙酰基肉毒碱/乙酰基肉毒碱（C3/C2）、丙酰基肉毒碱/游离肉碱（C3/CO）、蛋氨酸（Met））及尿液气相色谱（甲基丙二酸、甲基枸橼酸）检测数据及临床诊断进行分析。结果 56例甲基丙二酸血症中新生儿期发病的有24例、1岁内发病的有28例、1岁以上发病的有5例;临床表现以生长发育迟缓、抽搐、癫痫及代谢性酸中毒最多见;56例MMA尿中甲基丙二酸浓度在13.89～1739.58 nmol/（mg.肌酐）,平均为362.9、甲基枸橼酸浓度在1.81～106.08 nmol/（mg.肌酐）,平均为15.9;但是血串联质谱仪中游离肉碱低下的有24例（42.9%）,浓度在2.6～9.2μmol/L（10～52）,平均为6.3μmol/L、C3正常的有11例（19.6%）,浓度在0.63～4.45μmol/L（0.53～4.80）平均为3.6μmol/L、11例中C3/C2均增高,数值在0.37～2.2（0.05～0.35）,平均为0.89,其中有9例C3/CO增高,数值在0.23～1.95（0.02～0.22）,平均为0.81,其中有10例蛋氨酸低下,浓度在3.03-6.16μmol/L（9～42）,平均为4.23μmol/L。结论生长发育迟缓、抽搐、癫痫及代谢性酸中毒是MMA的主要临床表现;临床上诊断甲基丙二酸血症需要结合血串联质谱（LC-MS/MS）及尿液气相色谱（GC-MS）综合分析,以免发生漏诊。

Objective：In order to accumulate the diagnosis knowledge in analysis data of methylmalonic aidemia（MMA）,the aim of this study was to investigate the clinical manifestations and data of tandem mass spectrometer（LC-MS/MS）and gas chromatography mass spectrometry（GC-MS）in 56 cases of clinical infants. Methods：The data of 56 cases of clinical infants（male 27 cases,female 29 cases）were collected from January to December 2013 to analyze.The data includes MS/MS analysis（free cartinine（C0）,propionylcartinine（C3）,propionylcartinine（C3）/ acetylcarnitine（C2）,propionylcartinine（C3）/ free cartinine（C0）,methionine（MET））,GC-MS analysis（Methylmalonic,Methylcitrate）and clinical diagnosis;Results：Among 56 cases of MMA,24 and 28 cases got disease in a month and a year,respectively.The other 5 cases got disease over than one year.The most common symptoms are clinical manifestation with growth retardation,seizures epilepsy and metabolic acidosis.In 56 cases of MMA with GC-MS analysis,the concentration of Methylmalonic were determined was 13.89～1739.58 nmol/（mg·creatinine）and the average were determined was 362.9 nmol/（mg·creatinine）;the concentration of Methylcitrate was 1.81～106.08 nmol/（mg·creatinine）,and the average were determined was 15.9 nmol/（mg·creatinine）.However,in the analysis of LC-MS/MS,there were 24 cases（42.9%）that lower than normal value（C0）which concentration was 2.6～9.2 μmol/L（Reference Range：10～52 μmol/L）,the average was 6.3μmol/L.There were 11 cases（19.6%）were normal（C3）which concentration was 0.63～4.45μmol/L（Reference Range：0.53～4.80μmol/L）,）,the average was 3.6μmol/L.In these 11 cases,all C3/C2 increase and the ratio was 0.37～2.2（Reference Range：0.05～0.35）,the average was 0.89. In addition,9 cases C3/C0 increase and the ratio was 0.23～1.95（Reference Range：0.02～0.22）,the average was 0.81.Furthermore,10 cases MET were lower than normal value,that concentration was 3.03～6.16 μmol/L（Reference Range：9～42μmol/L）,the average was 4.23 μmol/L;Conclusion：Growth retardation,seizures,epilepsy and metabolic acidosis is the main clinical manifestations of MMA.In order to avoid missed delayed diagnosis,physician need to combine the LC-MS/MS and GC-MS comprehensive analysis.