目的 了解青岛地区新生儿中链酰基辅酶A脱氢酶缺乏症(MCADD)的患病率、临床特征及基因突变特点。方法 2015年1月-2018年8月利用串联质谱技术检测278 180例在青岛地区出生的新生儿干血滤纸片中酰基肉碱水平,对筛查出的疑似MCADD患儿通过尿有机酸检测,中链酰基辅酶A脱氢酶编码基因(ACADM)基因突变检测进行确诊。结果 共确诊4例中链酰基辅酶A脱氢酶缺乏症患儿,患病率0.001 4%(1/69 545)。患儿临床表现无明显异常,串联质谱检测均有中链酰基肉碱(C6~C10)升高。4例患儿共检测到7种ACADM基因突变,其中1例患儿为纯合突变,为c.1 040G>T(p.G347V)/ c.1 040G>T(p.G347V),其它3例为复合杂合突变,分别为:c.157C>T(p.R53C)/ c.709-1G>A;c.1 085G>A(p.G362E)/ c.461T>G(p.L154W);c.587G>A(p.G196E)/ c.387+1delG。尿有机酸检测1例患儿4-羟基-苯乙酸和4-羟基苯丙酮酸指标升高,肝功能异常。对患儿进行饮食指导,随访均未出现临床症状,体格及智力发育正常。结论 串联质谱新生儿筛查配合基因检测可以对MCADD早诊断,对预防疾病发作和提高患儿生活质量有重要意义。
Abstract
Objective To investigate the prevalence,clinical and gene mutation characteristics of medium chain acyl-CoA dehydrogenase deficiency(MCADD) in neonates in Qingdao area. Methods The acylcarnitine levels in the blood of 278 180 neonates from newborns screening program in Qingdao area were measured by tandem mass spectrometry.from January 2015 to August 2018.The suspected MCADD neonates were diagnosed by retrospective analysis of the urine organic acids and medium chain acyl-CoA dehydrogenase(ACADM) gene mutation. Results Four cases were diagnosed with MCADD,with the prevalence rate of 0.001 4%(1/69 545).There was no obvious abnormality in clinical manifestations,and the levles of medium chain acyl carnitine(C6-C10) increased in the four patients.Seven different mutations in the ACADM gene were identified in four cases.And one case was homozygous mutation:c.1 040G>T(p.G347V)/ c.1 040G>T(p.G347V).The other three cases were detected with compound heterozygous mutations,including c.157C>T(p.R53C)/ c.709-1G>A,c.1085G>A(p.G362E)/ c.461T>G(p.L154W)and c.587G>A(p.G196E)/ c.387+1delG.One case had increasing levels of 4-hydroxyphenylacetic acid and 4-hydroxyphenylpyruvate and hepatic insufficiency.Dietary guidance was given to the MCADD patients.No clinical symptoms were manifested and physical and intellectual development were normal during the follow-up period. Conclusion Inherited metabolic disease screening by tandem mass spectrometry for neonatal screening combined with gene detection can help early diagnosis of MCADD,which is of great significance to prevent the arrest of disease and improve the quality of life in MCADD children.
关键词
中链酰基辅酶A脱氢酶缺乏症 /
串联质谱 /
基因突变
Key words
medium chain acyl-CoA dehydrogenase deficiency /
tandem mass spectrometry /
gene mutation
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参考文献
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基金
青岛市医药科研指导计划(2016-WJZD085)
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