摘要
目的探讨枫糖尿病（MSUD）患者临床特点及早期诊断方法。方法于2003年1月至2011年12月对全国送检的1．4万临床遗传代谢病疑似患者进行检测，并对上海多家医院出生的41万名新生儿进行筛查。利用串联质谱检测血中亮氨酸和缬氨酸水平，利用气相色谱-质谱检测尿中支链α-酮酸水平，诊断MSUD依据为血亮氨酸、缬氨酸水平增高及尿支链α-酮酸水平增高。结果确诊33例MSUD患者，首诊年龄中位值为0．17岁（7d～30岁），发病高峰年龄段为2～30d，其中新生儿期发病者28例（84．8％）；首诊症状主要为喂养困难（14例）、反应差、嗜睡、抽搐等，确诊为经典型。经典型患者血亮氨酸水平及缬氨酸水平中位数（范围）分别为1901（458～5804）μmol／L及600（315～1617）μmol／L显著高于正常参考值（50～300μmol／L、60～250μmol／L，均P〈0．01）。尿2-羟基异戊酸、2．酮-异戊酸、2-酮-3-甲基戊酸、2-酮-异己酸、乙酰甘氨酸水平分别为262．5（5．4～624．3）、35．8（1．9～156．0）、133．8（7．4～611．5）、518．7（17．2～2121．2）及280．5（11．0～1087．9）均显著高于正常参考值（0、〈0．1、0、0及〈0．1）（均P〈0．01）。5例间歇型患者血亮氨酸、缬氨酸水平分别为402（348～958）μmol／L及556（322～808）μmol／L显著高于正常参考值（均P〈0．01），尿2-羟基异戊酸水平显著高于正常参考值（P〈0．01），其余支链α-酮酸水平稍升高。结论MSUD发病早、病情危重、临床表现缺乏特异性，血串联质谱氨基酸检测及尿气相色谱-质谱有机酸检测有助于此病的早期诊断。
Objective To explore the clinical characteristics and the diagnostic method of maple syrup urine disease （MSUD）. Methods From January 2003 to December 2011, a total of 14 000 patients with suspected inherited metabolism diseases were tested. The blood levels of leucine and valine of these patients were detected by tandem mass spectrometry. The urinary level of branchedchain α-ketoacids was tested by gas chromatographymass spectrometry. And the diagnosis was based on the elevated levels of leucine and valine in blood and branchedchain α-ketoacids in urine. Results Thirty-three MSUD patients were confirmed. Their median age of initial visit was 0. 17 years old （range： 7 days to 30 years old）. The peak onset age of them was 2 -30 days old, including 28 cases of neonatal onset （84. 8% ）. The presenting symptoms of 28 cases were feeding difficulties （ n = 14 ） , poor response, lethargy and seizures. Their median blood levels of leusine and valine （ 1901 （ 458 - 5804 ） and 600 （ 315 - 1617 ） μmol/L） were significantly higher than their normal levels （ （50 - 300） and （60 - 250） μmol/L, both P 〈0. 01 ）. Their urinary levels of 2-OH-isovalerieacid, 2-keto-isovalericaeid, 2-keto-3-methylvalericacid, 2-keto-isocaproie and acetylglycine （262. 5 （5.4 -624. 3 ）, 35.8 （1.9 - 156. 0 ）, 133.8 （7. 4 -611.5 ）, 518.7 （ 17.2 -2121.2 ） and 280. 5 （ 11.0 - 1087.9） respectively） significantly higher than their normal levels （0, 〈 0. 1, 0, 0, 〈 0. 1 respectively,all P 〈 0. 01 ）. In 5 intermittent MSUD patients, their blood levels of leucine and valine （402 （348 -958） and 556 （322 -808） μmol/L） were significantly higher than their normal levels（both P 〈0. 01 ）. The urinary level of 2-OH-isovalericacid was significantly higher than its normal levels （P 〈 0. 01 ） while the urinary levels of other α-ketoacids were normal. Conclusions The confirmation of MSUD remains difficult because of a lack of specific clinical features. The detections of tandem mass spectrometry and gas chromatography-mass spectrometry may aid its early diagnosis.
出处
《中华医学杂志》
CAS
CSCD
北大核心
2012年第40期2839-2842,共4页
National Medical Journal of China
基金
国家863高技术研究发展计划（2007AA022447）
上海市卫生局重大课题（2008ZD001）
上海市卫生局科研课题（2009210）
上海市科委重大课题（11DZ1950300）
关键词
枫糖尿病
串联质谱法
气相色谱-质谱法
诊断
Maple syrup urine disease
Tandem mass spectrometry
Gas chromatography-mass spectrometry
Diagnosis
