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

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.

Key words: mthylmalonic acidemia, homocysteine, tandem mass dpectrometry, MUT gene, MMACHC gene, mutation