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目的:了解陕西地区新生儿甲基丙二酸血症的发病率、生化分型和基因突变谱。方法:回顾性分析2014年1月至2019年12月在西北妇女儿童医院进行新生儿筛查的146 152例新生儿中确诊为甲基丙二酸血症的患儿的临床表现和随访情况，以及酰基肉碱水平和基因突变情况。根据是否合并同型半胱氨酸升高，分为单纯型和合并型甲基丙二酸血症，并与复查时排除诊断的患儿（对照组）比较。采用Kruskal-Wallis检验和Mann-Whitney n U检验进行统计学分析。n 结果:（1）共21例患儿确诊，发病率为1/6 960；单纯型11例（52.4%），合并型10例（47.6%）。8例单纯型患儿在1月龄以内发病，主要临床表现为喂养困难、呕吐、嗜睡、反应差和感染，其中5例患儿死亡。合并型患儿确诊前均未出现典型临床表现，随访发育均未见异常。（2）单纯型和合并型患儿的血丙酰肉碱、丙酰肉碱/乙酰肉碱比值及丙酰肉碱/游离肉碱比值均高于对照组[n M（min~max），9.26 μmol/L（3.70~37.78 μmol/L）、7.27 μmol/L（3.58~13.62 μmol/L）与4.51 μmol/L（1.48~8.69 μmol/L），n H=23.239；1.12（0.32~2.43）、0.74（0.36~1.90）与0.25（0.09~0.45），n H=47.061；0.94（0.12~1.92）、0.56（0.18~1.03）与0.17（0.06~0.38），n H=36.868；n P值均G为未报道的突变位点，为临床意义不明确的突变。合并型最常见的突变为n MMACHC基因c.609G>A（p.Trp203Ter）和c.567dupT（p.Ile190fs），携带频率均为20.0%。检出c.430-2A>C和c.648_650delAGA（p.216_217delSEinsS）为未报道的突变，为疑似致病突变。n 结论:本地区甲基丙二酸血症并不罕见。单纯型甲基丙二酸血症患儿病情更重。n MMACHC基因c.609G>A和c.567dupT以及n MMUT基因c.323G>A等突变热点的发现，为后续开展基因筛查、遗传咨询及产前诊断，有效降低甲基丙二酸血症的致死率和致残率奠定基础。n “,”Objective:To analyze the incidence, biochemical and molecular characteristics, and gene mutation spectrum of neonatal methylmalonic acidemia (MMA) in Shaanxi province.Methods:This study involved 146 152 newborns undergoing neonatal screening for methylmalonic acidemia by tandem mass spectrometry in Northwest Women's and Children's Hospital from January 2014 and December 2019. Clinical manifestations and follow-up data of newborns diagnosed with MMA and their acylcarnitine profiles and gene mutations were analyzed. According to whether they had elevated homocysteine or not, these patients were divided into two groups, the complicated group and the isolated MMA group. The control neonates were those excluded from having methylmalonic acid by re-examination. Kruskal-Wallis and Mann-Whitneyn U test was conducted for statistical analysis.n Results:(1) Twenty-one cases of MMA were confirmed with an incidence of 1/6 960, including 11 cases (52.4%) of isolated MMA (isolated MMA group) and 10 (47.6%) complicated by elevated homocysteine (complicated group). Eight patients in the isolated group had symptoms within one month after birth, mainly feeding difficulties, vomiting, drowsiness, poor response and infection, and five died. Patients in the complicated group were all diagnosed before developing typical clinical symptoms, and no developmental abnormalities were reported during follow-up. (2) Blood propionyl carnitine and its ratios to acetylcarnitine and free carnitine in the isolated MMA and complicated groups were higher than those in the control group [n M (min-max), 9.26 (3.70-37.78) μmol/L and 7.27 μmol/L (3.58-13.62 μmol/L) vs 4.51 μmol/L (1.48-8.69 μmol/L), n H=23.239; 1.12 (0.32-2.43) and 0.74 (0.36-1.90) vs 0.25 (0.09-0.45), n H=47.061; 0.94 (0.12-1.92) and 0.56 (0.18-1.03) vs 0.17 (0.06-0.38), n H=36.868; all n PG, with unidentified clinical significance, was also found. The most common mutations in the complicated group were c.609G>A (p.Trp203Ter) and c.567dupT (p.Ile190fs) in then MMACHC gene, and the positive rates were both 20.0%. Moreover, two unreported variants, c.430-2A>C and c.648_650delAGA (p.216_217delSEinsS), were detected and suspected to be pathogenic.n Conclusions:MMA is not uncommon in Shaanxi province. Children with isolated MMA tend to be more severe clinically. The identification of hotspot mutations, including c.609G>A (p.Trp203Ter) and c.567dupT (p.Ile190fs) inn MMACHC gene and c.323G>A (p.Arg108His) inn MMUT gene, provides a foundation for further genetic screening, counseling, and prenatal diagnosis, and is conducive to reduce the mortality and disability rate of neonatal MMA.n