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中国循证儿科杂志

中国循证儿科杂志 ›› 2020, Vol. 15 ›› Issue (6): 459-462.

• 论著 • 上一篇    下一篇

婴儿期起病的甲基丙二酸血症41例病例系列报告

邓冬立1,3,肖非凡1,3,吴冰冰1,孙卫华1,杨琳2,陆 炜2,周文浩1   

  1. 复旦大学附属儿科医院 上海，201102，1 分子医学中心，2 内分泌遗传代谢科；3 共同第一作者
  • 收稿日期:2020-09-17 修回日期:2020-11-11 出版日期:2020-12-25 发布日期:2020-12-25
  • 通讯作者: 杨琳;陆炜

41 cases of infants with methylmalonic acidemia: A case series report

DENG Dongli1,3, XIAO Feifan1,3, WU Bingbing1, SUN Weihua1, YANG Lin2, LU Wei2, ZHOU Wenhao1   

  1. Children's Hospital of Fudan University, Shanghai 201102, China, 1 Center for Molecular Medicine, 2 Department of Endocrinology and Inherited Metabolic Diseases； 3 Co-first authors
  • Received:2020-09-17 Revised:2020-11-11 Online:2020-12-25 Published:2020-12-25
  • Contact: YANG Lin; LU Wei

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摘要： 目的:总结婴儿期起病的甲基丙二酸血症（MMA）患儿的首发临床特征和基因突变情况，分析表型与基因型的关联性。方法:纳入2016年6月至2019年6月经复旦大学附属儿科医院分子医学中心基因检测发现携带MMA已知致病基因的致病或可疑致病变异的婴儿，截取患儿就诊的主要原因、临床信息和基因检测结果，按照不同致病基因分组比较患儿的临床表型。结果:41例中男26例，中位起病时间为21日龄，新生儿期就诊25例，28 d至6个月就诊12例，~12个月就诊4例；主要就诊原因为生后反应差（24例）和遗传代谢病串联质谱筛查疑似MMA（8例）。共检出MUT基因和MMACHC基因的47种致病/可疑致病变异。MUT基因热点致病变异为c.729_730insTT、c.323G>A和c.1677-1G>A；MMACHC基因热点致病变异为c.609G>A、c.567dupT和c.80A>G。33例有临床表现的患儿中，22例携带MUT基因变异（MUT组），11例携带MMACHC变异（MMACHC组）；2组最常见的表型均为肌张力异常、呼吸系统异常和喂养困难，差异均无统计学意义。MUT组更易出现酸中毒（50.0% vs 9.1%，P=0.027），MMACHC组更易出现心肌受累（36.4% vs 4.5%，P=0.037）。5例患儿放弃治疗后死亡。结论:婴儿期出现反应差、肌张力异常、呼吸系统异常及喂养困难的患儿，应警惕甲基丙二酸血症的可能性。MMA患儿携带MUT基因突变更易出现酸中毒症状，携带MMACHC基因突变更易合并心肌受累。

Abstract: Objective: To summarize initial clinical characteristics and gene mutations of infants with methylmalonic acidemia (MMA) and to analyze genotype-phenotype correlation. Methods: Infants diagnosed as MMA by genetic testing were recruited from June 2016 to June 2019 in Center for Molecular Medicine of Children's Hospital of Fudan University. Clinical characteristics and genetic test results were included for analysis. We compared patients' phenotypes based on genotype. Results: Forty-one infants were included in this study. Of them, twenty-six patients were males and the median age of onset was 21 days. Totally, 25 patients referred to hospital at neonatal time, 12 patients referred to hospital in 28 days to 6 months of age, and 4 patients referred to hospital in 6 months to 12 months of age. The most common chief complaints were poor postnatal response (24 patients) and suspected MMA by newborn screen (8 patients). Two genes (MUT and MMACHC) were detected in these patients and forty-seven kinds of pathogenic or likely pathogenic variants were detected. The hot mutations included c.729_730insTT, c.323G>A, and c.1677-1G>A for MUT gene. For MMACHC gene, c.609G>A, c.567dupT, and c.80A>G were hot mutations. A total of thirty-three patients presented clinical features, 22 patients detected with MUT gene variations and 11 patients detected with MMACHC gene variations. For two gene variations, the common clinical characteristics were dystonia, abnormal breathing, and feeding intolerance. No statistical differences were found in these two groups. Compared with patients with MMACHC mutations, patients with MUT mutations were more easily presented acidosis (50.0% vs 9.1%, P=0.027); however, patients with MMACHC mutations were easily presented cardiomyopathy than patients with MUT mutations (36.4% vs 4.5%, P=0.037). A total of five patients gave up treatments and died. Conclusion: Infants, who presented with poor response, dystonia, abnormal breathing, and feeding intolerance, should be consider the possibility of MMA.MMA patients with MMACHC variations were easily presented cardiomyopathy and patients with MUT variations were easily presented acidosis.