http://jcp.xinhuamed.com.cn:8080/CN/1000-3606/home.shtml 儿童危重型甲基丙二酸血症临床特点及基因分析

临床儿科杂志 ›› 2019, Vol. 37 ›› Issue (12): 885-.doi: 10.3969/j.issn.1000-3606.2019.12.002

• 遗传、代谢、内分泌疾病专栏 • 上一篇    下一篇

儿童危重型甲基丙二酸血症临床特点及基因分析

刘敏,崔利丹,王琪   

  1. 郑州大学附属儿童医院 河南省儿童医院 郑州儿童医院 (河南郑州 450000)
  • 发布日期:2020-02-03
  • 通讯作者: 王琪 电子信箱:shueijx@sina.com

Clinical characteristics and gene analysis of critical methylmalonic acidemia in children

LIU Min, CUI Lidan, WANG Qi   

  1. Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou 450000, Henan, China
  • Published:2020-02-03

摘要: 目的 分析危重型甲基丙二酸血症的临床及基因学特点。方法 回顾分析2015年9月至2018年12月34例 危重型甲基丙二酸血症患儿的临床资料,其中11例行基因检测。结果 34例患儿中男18例、女16例,中位发病年龄为 11.5个月。所有患儿均存在2个及以上脏器功能障碍或衰竭,除常见血液系统、肝、肾、心、肺血管及神经系统损害外,11 例合并纤维蛋白原水平降低, 3例合并第四脑室中、侧孔先天性闭锁脑发育畸形(Dandy-Walker畸形)。11例行基因检测的 患儿中, 9例为MMACHC基因突变,c.609G>A位点突变为合并型甲基丙二酸血症热点突变,其中2例行基因检测的脑发 育畸形患儿均存在c.609G>A位点突变;另2例为单纯型甲基丙二酸血症,均为甲基丙二酰辅酶A变位酶(MUT)基因突 变所致。结论 危重型甲基丙二酸血症患儿神经损害最常见,部分可合并脑发育畸形,且可能与c.609G>A基因位点突变 有关;可合并纤维蛋白原水平降低

关键词: 甲基丙二酸血症; 纤维蛋白原; dandy-Walker畸形

Abstract:  Objective To analyze the clinical and genetic characteristics of critical methylmalonic academia. Methods The clinical data of 34 cases of critically methylmalonic acidemia from September 2015 to December 2018 were retrospectively analyzed, among which 11 cases underwent genetic testing. Results In the 34 cases (18 males and 16 females) median age was 11.5 months. All the children had 2 or more organ dysfunction or failure. In addition to the damages commonly seen in blood system, liver, kidney, heart, pulmonary vascular and nervous system, 11 patients had decreased fibrinogen level and 3 patients had congenital atresia of the middle and lateral foramen of the fourth ventricle (Dandy-Walker malformation). In the 11 children who underwent genetic testing, 9 had mutations in MMACHC gene, and c.609G>A mutation was a hot spot mutation in combined methylmalonic acidemia. Two children with brain developmental malformation had mutations of c.609G>A. The other 2 cases were simple methylmalonic acidemia, both caused by the mutation in methylmalonyl coenzyme A mutase (MUT) gene. Conclusions Neurological damage is most common in children with critical methylmalonic acidemia, and some children may be associated with brain developmental malformations, which may be related to c.609G>A locus mutation. The level of fibrinogen can be decreased.

Key words:  methylmalonic acidemia; fibrinogen; Dandy-Walker malformation