合并溶血尿毒症综合征的甲基丙二酸血症患儿的临床及遗传学分析  

Clinical and genetic analysis of methylmalonic acidemia in children with hemolytic uremic syndrome

作　　者：万灵 陈朝英[1] 涂娟[1] 李华荣[1] 陈倩[2] Wan Ling;Chen Chaoying;Tu Juan;Li Huarong;Chen Qian(Department of Nephrology,Children's Hospital Affiliated to Capital Institute of Pediatrics,Beijing 100020,China;Department of Neurology,Children's Hospital Affiliated to Capital Institute of Pediatrics,Beijing 100020,China)

机构地区：[1]首都儿科研究所附属儿童医院肾脏内科,北京100020 [2]首都儿科研究所附属儿童医院神经内科,北京100020

出　　处：《中华肾脏病杂志》2024年第7期553-557,共5页Chinese Journal of Nephrology

摘　　要：该研究为回顾性研究。分析2010年1月至2022年12月于首都儿科研究所附属儿童医院住院的13例合并溶血尿毒症综合征(hemolytic uremic syndrome,HUS)的甲基丙二酸血症(methylmalonic acidemia,MMA)患儿的病历资料,探讨MMA合并HUS(MMA-HUS)的临床特点及遗传学特征。MMA发病年龄为18 d至5岁,早发型11例,晚发型2例;单纯型MMA 4例,合并型MMA 9例;继发高血压7例,继发肺动脉高压3例。行基因检测7例,MMUT基因变异1例,MMACHC基因变异6例,变异位点均来源于父母,均为已知致病性变异;其中5例存在MMACHC基因c.80A>G杂合变异,且均伴有心血管受累。经病因及对症治疗后6例病情好转,7例死于多器官衰竭,死亡病例均为早发型MMA。该研究显示,MMA-HUS更常见于早发型MMA,且病情重、病死率高,其预后可能与基因型、诊断及治疗时机等多因素相关。MMACHC基因的c.80A>G变异可能与HUS及心血管受累有关。It was a retrospective study.The case data of thirteen patients diagnosed with methylmalonic acidemia(MMA)combined with hemolytic uremic syndrome(HUS)hospitalized at the Children's Hospital Affiliated to Capital Institute of Pediatrics from January 2010 to December 2022 were analyzed,to explore clinical and genetic characteristics of MMA combined with HUS(MMA-HUS).The onset age of MMA was 18 days to 5 years old,with 11 patients of early onset and 2 patients of late onset,4 patients of simple MMA and 9 patients of combined MMA,and 7 patients of secondary hypertension and 3 patients of secondary pulmonary arterial hypertension.Among 13 patients,7 patients underwent genetic testing,with 1 patient of MMUT gene mutation and 6 patients of MMACHC gene mutation.The mutation sites were all from their parents and all were known pathogenic variants.Among them,5 patients had MMACHC gene c.80A>G heterozygous variation,accompanied by cardiovascular involvement.After etiological and symptomatic treatment,6 patients improved,7 patients died of multiple organ failure,and all the deaths were early-onset MMA.This study shows that MMA-HUS is more common in early-onset MMA,with a severe condition and a high mortality rate.Its prognosis is related to multiple factors such as genotype,diagnosis and treatment timing.c.80A>G variation of MMACHC gene may be related to HUS and cardiovascular involvement.

关 键 词：儿童 溶血尿毒症综合征 甲基丙二酸 甲基丙二酸血症 同型半胱氨酸血症 

分 类 号：R726.9[医药卫生—儿科]