21例枫糖尿病患者血串联质谱及尿液气相色谱检测数据分析及文献复习

Data analysis of serum tandem mass spectrometry and urine gas chromatography examination and literature review of 21 cases of maple syrup urine disease

目的探讨枫糖尿病(MSUD)患者血串联质谱亮氨酸、缬氨酸、LEU/PHE、VAL/PHE及尿液气相色谱2-酮-异戊酸、2-酮-异己酸、2-酮-3-甲基戊酸的检测数据及临床诊断为诊断枫糖尿病积累经验。方法分析2013年1月份至2017年5月份21例枫糖尿病临床患儿的血串联质谱(亮氨酸、缬氨酸、LEU/PHE、VAL/PHE)及尿液气相色谱(2-酮-3-甲基戊酸、2-酮-异戊酸、2-酮-异己酸)检测数据及临床诊断进行分析。结果 21例枫糖尿病患者中新生儿期发病的有15例(71.4%)、1岁以内发病的有3例(14.3%)、1岁以上发病的有3例(14.3%);临床表现常见喂乳困难、抽搐、反应差、尿异味、肌张力异常,实验室常规检查以代谢性酸中毒、高血氨、乳酸增高最多见;21例血串联质谱检测亮氨酸浓度在579.39～7172.76μmol/L(93～365)、缬氨酸浓度在325.97～1247.23μmol/L(61～307)、LEU/PHE在8.14～86.97(1.5～6.19)、VAL/PHE在1.88～19.28(1.3～5.9);15例枫糖尿病患者中尿液气相色谱检测2-酮-异戊酸、2-酮-异己酸、2-酮-3-甲基戊酸均呈现不同程度增高,2-酮-异己酸浓度在0.59～817.07nmol/(mg.肌酐)(<0.48)、2-酮-异戊酸浓度在6.79～83.15nmol/(mg.肌酐)(<0.1)、2-酮-3-甲基戊酸浓度在0.59～95.63nmol/(mg.肌酐)(<0.28)。结论枫糖尿病多在新生儿期发病,临床表现以喂乳困难、抽搐、反应差、尿异味、肌张力异常为主;常规实验室检查可见代谢性酸中毒及血氨增高;血串联质谱以亮氨酸、缬氨酸显着增高、尿检2-酮-异己酸、2-酮-异戊酸、2-酮-3-甲基戊酸增高为诊断枫糖尿病的特异性标志物,临床上诊断枫糖尿病需将两种检测方法结合以减少漏诊及误诊。

Objective：To investigate the correlation between blood tandem mass spectrometry of leucine,valine,LEU/PHE,VAL/PHE and urine 2-Keto-isovalericacid,2-Keto-isocaproic,2-Keto-3-methylvaleric acid test data and clinical diagnosis to accumulation experience in clinical diagnosis of maple syrup urine disease. Methods：Analyze the blood levels of leucine,valine,LEU/PHE and VAL/PHE in 21 children with maple syrup urine disease from January 2013 to May 2017 with gas chromatography（2-Keto-isovalericacid,2-Keto-isocaproic,2-Keto-3-methylvaleric acid）detection data and clinical diagnosis. Results：In 21 cases of MSUD,there were 15 cases（71.4%）in neonatal period,3 cases（14.3%）in 1 year old and 3 cases（14.3%）of older than 1 year old. Clinical symptoms include feeding difficulties,convulsions,poor response,urine odor,dystonia,routine laboratory tests show metabolic acidosis,hyperammonemia,lactic acid increased the most common;21 cases of blood tandem mass spectrometry leucine concentrations of 579.39～7172.76μmol/L（93-365）,valine concentration was 325.97～1247.23μmol/L（61-307）,LEU/PHE was 8.14～86.97（1.5-6.19）and VAL/PHE was 1.88～19.28（1.3-5.9）. 15 cases of MSUD Detection of urine gas chromatography in 2-Keto-isovaleric acid,2-Keto-isocaproic,2-Keto-3-methylvaleric acid showed all different degrees of increase. The concentration of 2-Keto-isocaproic ranged from0.59～817.07 nmol/（mg. Creatinine）（〈0.48）,2-keto-isovaleric acid ranged from 6.79～83.15 nmol/（mg. Creatinine）（〈0.1）,2-keto-3-methylpentanoic acid ranged from 0.59～95.63 nmol/（mg. Creatinine）（〈0.28）. Conclusions：Most MSUD outbreak appear in the neonatal period. The clinical symptoms are mainly feeding difficulties,convulsions,poor response,Odors of urine and dystonia. Metabolic acidosis and blood ammonia increase can be seen in routine laboratory tests. The diagnosis of MSUD specific markers of the clinical diagnosis is that Serum Tandem Mass Spectrometry Serine indicates leucine and valine to be increased significantly,and also urinary 2-keto-isocaproic acid,2-keto-isovaleric acid,2-keto-3-methylpentanoic acid increased. Combining two test methods for MSUD diagnosis in clinical diagnose can reduce missed diagnosis and misdiagnose.