串联质谱技术在有机酸血症鉴别诊断中的应用  

Study of application of the tandem mass spectrometry in the differential diagnosis of organic acidemias

作　　者：韩连书[1] 高晓岚[1] 叶军[1] 邱文娟[1] 王瑜[1] 顾学范[1] 

机构地区：[1]上海交通大学医学院附属新华医院上海市儿科医学研究所,上海200092

出　　处：《临床儿科杂志》2006年第12期970-974,共5页Journal of Clinical Pediatrics

基　　金：上海市重点学科建设项目(No.T0204);上海市科委科研基金资助项目(No.024119021)

摘　　要：目的探讨串联质谱技术在有机酸血症诊断和鉴别诊断中的作用。方法对2566例遗传性代谢病高危儿童的干血滤纸片进行串联质谱分析,结合尿气相色谱质谱有机酸分析、酶活性测定和基因突变分析,诊断有机酸血症。比较不同有机酸血症间的串联质谱结果差异。结果共确诊有机酸血症82例(3.2%),其中甲基丙二酸血症(MMA)44例,丙酸血症(PA)10例,生物素酶缺乏症4例和全羧化酶合成酶缺乏症2例;患儿丙酰肉碱(propinoylcar-nitine,C3)水平均高于健康儿童上限值(4.0μmol/L)。PA和MMA患儿C3与游离肉碱(C0)比值(C3/C0)、C3与乙酰肉碱(C2)比值(C3/C2)也高于健康儿童上限值;PA患儿同时伴有甘氨酸增高,甲基丙二酸血症患儿甘氨酸正常;生物素酶缺乏症和全羧化酶合成酶症患儿伴3"羟基"异戊酰肉碱(3"hydyoxyl"isovalerylcarnitine,C5"OH)水平增高;3"甲基巴豆酰辅酶A羧化酶缺乏症(5例)、3"羟基"3"甲基戊二酰辅酶A裂解酶缺乏症(3例)和β"酮硫解酶缺乏症(4例)患儿C5"OH水平也增高,前两种疾病仅表现为C5"OH增高,后一种疾病同时伴有异戊烯酰基肉碱水平增高;异戊酸血症5例,仅表现为异戊酰肉碱(C5)增高;戊二酸血症(GA)"Ⅰ型(3例)仅表现为戊二酰肉碱(C5DC)增高,GA"Ⅱ型(2例)除C5DC增高外,伴有多种酰基肉碱增高,两者可作鉴别。结论通过串联质谱酰基肉碱、酰基肉碱比值和氨基酸分析,可对部分有机酸血症进行诊断和鉴别诊断;部分有机酸血症需结合尿气相色谱质谱有机酸分析进行诊断。Objectives To investigate the effect of tandem mass spectrometry on the differential diagnosis of organic acidemias. Methods Combined with gas- chromatography mass spectrometry,enzymetic activity determination,genomic mutation analysis, tandem mass spectrometry was used for 2 566 children with high risk of genetic inborn metabolism diseases to confirm the diagnosis of organic acidemias. The resuhs were also compared among the patients with different diseases. Results Eighty-two patients were diagnosed as organic academia, including 44 patients with methylmalonic academia （MMA）, 10 with propionic academia（PA）,4 with biotinidase deficiency （BTD）,and 2 with holocarboxylase sythetase deficiency . The propinoylcarnitine （C3） level in all these patients was higher than the upper limit value of normal control （4.0 μmol/L）. The ratio of C3/C0 （free carnitine）and C3/C2（acytylcarnitine）also exceed the upper limit normal level in patients with PA and MMA. The level of glycine was also elevated in PA patients, but normal in MMA patients. While the 3-hydyoxyl- isovalerylearnitine （C5-OH） level increased signitieantly in the patients with BTD and holocarboxylase synthetase deficiency. In addition ,increased C5- OH were also identified in patients with 3- methyl- crotonyl - CoA carboxylase deficiency （MCC, 5 cases ）, 3- hydroxy- 3 - methylglutaryl - CoA lyase deficiency （HMG, 3 cases ）, and beta-keto thiolase deficiency （BKT,4 cases）. C5-OH was the only finding in the former two diseases,but in patients with BKT,senecioyl-earnitine was also elevated significantly. Only was the isovalerylcarnitine level increased in 5 cases of isovalerie acidemias. In 3 cases with glutarie aeidemia type Ⅰ ,only was glutarylearnitine increased. But in 2 cases with glutarie acidemia type Ⅱ ,variety of the aeylcarnitines was also increased. Conclusions The organic acidemias can be identified by analysis of acylcarnitines amino acids and the ratio of acylcarnitines with tandem mass spectrometry,which

关 键 词：串联质谱 有机酸血症 酰基肉碱 鉴别诊断 

分 类 号：R589[医药卫生—内分泌]