通过新生儿筛查及临床确诊的3-羟基异戊酰肉碱代谢异常相关疾病患者的疾病谱分析  

Analysis of disease spectrum for abnormal 3-hydroxyisovalerylcarnitine metabolism identified through newborn screening and clinical diagnosis

作　　者：杨奕[1] 邱文娟[1] 张惠文[1] 梁黎黎[1] 陆德云 张开创 陈婷[1] 徐烽[1] 顾学范[1] 韩连书[1] Yang Yi;Qiu Wenjuan;Zhang Huiwen;Liang Lili;Lu Deyun;Zhang Kaichuang;Chen Ting;Xu Feng;Gu Xuefan;Han Lianshu(Department of Pediatric Endocrinology and Genetic Metabolism,Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,Shanghai Institute for Pediatric Research,Shanghai 200092,China)

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,儿内分泌遗传代谢科,上海200092

出　　处：《中华医学遗传学杂志》2023年第12期1466-1471,共6页Chinese Journal of Medical Genetics

基　　金：上海市卫生健康委员会科研项目(202140346)。

摘　　要：目的探讨我国3-羟基异戊酰肉碱(C5OH)相关疾病的新生儿筛查和临床确诊患者的疾病谱及其相互鉴别的要点,以提高临床医师对这类疾病的认识。方法收集2004年2月至2022年1月在上海交通大学医学院附属新华医院的85例新生儿筛查以及临床确诊的C5OH升高的患者的临床资料,对其临床表现、血串联质谱、尿气相色谱质谱检测的特异性指标及基因检测结果进行分析。结果在85例患者中,有46例(54.1%)源自新生儿筛查,39例(45.9%)为临床诊断的病例,共诊断出5种疾病,其中多种羧化酶缺乏症28例(32.9%)、3-甲基巴豆酰辅酶A羧化酶缺乏症29例(34.1%)、3-甲基戊烯二酸尿症4例(4.7%)、3-羟基-3-甲基戊二酸尿症7例(8.2%)、β-酮硫解酶缺乏症17例(20.0%)。常见的临床表现包括急性起病、纳差、呕吐、腹泻、呼吸异常、意识障碍、抽搐及发育落后等。结论在C5OH相关的疾病中,通过新生儿筛查确诊的患者以3-甲基巴豆酰辅酶A羧化酶缺乏症最为常见,其次为β-酮硫解酶缺乏症、多种羧化酶缺乏症等。临床发病后确诊的患者以多种羧化酶缺乏症最为常见,其次为β-酮硫解酶缺乏症、3-羟基-3-甲基戊二酸尿症等。这类疾病具有较强的异质性,需结合其临床特点与血酰基肉碱、尿有机酸水平及基因检测结果以明确诊断。Objective To explore the disease spectrum for abnormal 3-hydroxyisovalerylcarnitine(C5OH)metabolism identified through newborn screening and clinical diagnosis patients and the key points for differential diagnosis so as to raise the awareness of pediatricians for such diseases.Methods Clinical data of 85 neonates with abnormal C5OH metabolism identified from February 2004 to January 2022 at Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine were collected.Their clinical manifestations and results of tandem mass spectrometry(MS/MS),gas chromatography mass spectrometry(GC-MS)and genetic testing were retrospectively analyzed.Results Among the 85 cases,46(54.1%)were identified by neonate screening,whilst 39(45.9%)were clinically diagnosed patients.Five diseases were diagnosed,including 28 cases with multiple carboxylase deficiency(MCD,32.9%),29 cases with 3-methylcrotonyl-coenzymeAcarboxylasedeficiency(MCCD,34.1%),4 cases with 3-methylglutaconic acid(3-MGA,4.7%),7 cases with 3-hydroxy-3-methylglutaric acid(3-HMG,8.2%),and 17 cases with beta-ketothiolase deficiency(BKD,20.0%).The disorders were characterized by sudden onset,anorexia,vomiting,diarrhea,abnormal breathing,consciousness disorder,spasm and developmental delay.Conclusion Among newborns with abnormal C5OH metabolism,MCCD is the most common disorder,which was followed by BKD and MCD.For patients with abnormal C5OH metabolism,MCD is the most common,followed by BKD and 3-HMG.C5OH related diseases have great heterogeneity.Combination of blood acylcarnitine levels,urinary organic acid levels and genetic testing based on clinical characteristics can help to attain the diagnosis.

关 键 词：3-羟基异戊酰肉碱 新生儿筛查 遗传代谢病 串联质谱 气相色谱质谱 

分 类 号：R722.1[医药卫生—儿科]