目的 分析甲基丙二酸血症(MMA)患儿的临床表型、基因突变类型以及不同类型治疗效果,为该病的产前诊断提供科学依据。方法 利用串联质谱技术对菏泽市2015年5月-2019年12月出生的210 319名新生儿进行筛查,结合尿气相色谱质谱检测及二代测序技术,将确诊的88例患儿分为单纯型MMA患儿和MMA合并同型半胱氨酸血症,进行相应治疗,并采用配对样本t检验对患儿治疗前后进行比较分析。结果 88例MMA患儿中79例为MMA合并同型半胱氨酸血症,9例为单纯型MMA,49例患儿行基因测序,其中MUT基因突变位点13个,包括3个未报道突变:c.389G>A:1963C>T、c.2009G>T、c.1233_1235delCAT;MMACHA基因突变位点20个,包括5个未报道突变:c.481C>T、c.568dupT、c.57delT、c.471G>A、c.IVS2+149C>T。78例MMA合并同型半胱氨酸血症患儿治疗后较治疗前血中丙酰肉碱(C3)值和尿中甲基丙二酸值显著下降,差异有统计学意义(P<0.05)。结论 新生儿遗传代谢病筛查能对MMA早发现、早诊断、早治疗,并降低其死亡率和致残率。基因检测有助于MMA分型诊治,不同基因型的临床表型以及对治疗反应不同。新发突变位点,不仅丰富了我国MMA患儿基因突变谱,而且为先证者家系提供产前诊断。
Abstract
Objective To analyze the clinical phenotype, gene mutation type and different types of treatment effects of children with methylmalonic acidemia (MMA). Methods A total of 210 319 newborns born in Heze City from May 2015 to December 2019 were screened by using tandem mass spectrometry technology combined with urine gas chromatography mass spectrometry and second-generation sequencing technology. And 88 diagnosed patients were divided into simple MMA children and MMA children combined with homocysteine, and were given responding treatment accordingly. Paired sample t test was used to compare and analyze the data before and after treatment. Results Of the 88 children with MMA, 79 were MMA with homocysteine, 9 were simple MMA. And 49 children performed genetically sequencing, indicating 13 mutation sites of MUT gene and 20 mutation sites of MMACHA gene. Finally 3 unreported mutations were found in MUT gene, including c.389G>A:1963C>T, c.2009G>T, c.1233_1235delCAT. And 5 unreported mutations were found in MMACHA gene, including c.481C>T, c.568dupT, c.57delT, c .471G>A, c.IVS2+149C>T. After treatment, 78 children with MMA combined with homocysteine had significantly lower blood propionylcarnitine (C3) value and urine methylmalonic acid value(P<0.05). Conclusions Newborn genetic metabolic disease screening can detect, diagnose, and treat MMA children early, and reduce the mortality and disability rate of MMA children. Genetic testing is helpful for the diagnosis of MMA typing and treatment plans. The clinical phenotype of different genotypes and the response to treatment are different. And the new mutation sites not only enrich the gene mutation spectrum of children with MMA, but also provide prenatal diagnosis for proband families.
关键词
甲基丙二酸血症 /
同型半胱氨酸血症 /
串联质谱 /
MUT基因 /
MMACHC基因 /
突变
Key words
mthylmalonic acidemia /
homocysteine /
tandem mass dpectrometry /
MUT gene /
MMACHC gene /
mutation
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基金
2019年江苏省高层次创业人才引进计划(双创计划)资助项目(2019)
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