郑州大学附属儿童医院甲基丙二酸血症158例临床资料分析

Analysis of clinical data of 158 patients with methylmalonic acidemia in Children’s Hospital Affiliated to Zhengzhou University

目的分析郑州大学附属儿童医院收治的甲基丙二酸血症(methylmalonic acidemia,MMA)患儿临床和遗传学特点。方法回顾性研究2013年6月至2018年3月郑州大学附属儿童医院收治的158例MMA患儿临床及基因突变特点,依据生化检测结果分型、治疗、随访。结果158例MMA患儿首诊年龄1 d至13岁,28例(17.7%)为单纯型MMA,130例(82.3%)为MMA合并同型半胱氨酸血症。76例(48.1%)经新生儿筛查诊断,42例随访期间未出现急性代谢紊乱相关症状,但仅20例发育正常,22例存在运动语言发育落后;34例发病者中1岁以内发病30例(88.2%)。82例(51.9%)经临床诊断,1岁以内发病60例(56.9%)。首发临床表现依次有喂养困难、嗜睡、呕吐、体重不增及抽搐。126例接受基因检测,其中103例(81.7%)为MMACHC基因变异,共检出突变200个,最常见为c.609G>A(p.W203X)和c.80A>G(p.Q27R)。23例(18.3%)为MUT基因变异,共检出突变46个,最常见为c.1106G>A(p.R369H)。结论郑州大学附属儿童医院MMA主要类型为MMA合并同型半胱氨酸血症,MMACHC基因突变最常见,c.609G>A(p.W203X)和c.80A>G(p.Q27R)可能为河南地区热点突变。经新生儿筛查诊断者较多,预后相对较好,经临床诊断者多数遗留精神运动发育迟缓。

Objective To analyze the clinical and genetic characteristics of child patients with methylmalonic acidemia(MMA)in Children’s Hospital Affiliated to Zhengzhou University.Methods The clinical characteristics and genetic mutations of 158 patients were retrospectively studied,who were treated in Children’s Hospital Affiliated to Zhengzhou University from June 2013 to March 2018.The genotyping,treatment and follow-up were made based on chemobiological results.Results The onset age of these 158 patients ranged from 1 day to 13 years old.Twenty-eight patients(17.7%)were diagnosed with isolated MMA,while the other 130 cases(82.3%)were suffering from MMA combined with homocysteinemia.Among 76 patients(48.1%)diagnosed through newborn screening,forty-two cases had no obvious symptom related to acute metabolic disorder and 20 of them had normal psychomotor development.Twenty-two children had retarded development in motor and language.Thirty(88.2%)of 34 symptomatic patients appeared abnormal clinical presentations within the first year.Eighty-two cases(51.9%)were clinically diagnosed,and 60 of them(56.9%)had first onset in infancy.The first clinical manifestations were,in turn,feeding difficulty,lethargy,vomiting,difficulty in weight gain and convulsion.Totally 126 patients accepted gene testing,among which a total of 200 MMACHC mutations were detected in 103 cases(81.7%).The most common mutations were c.609 G>A(p.W203 X),then was c.80 A>G(p.Q27 R).Totally 46 MUT mutations were found in 23 cases(18.3%),and the most common mutation was c.1106 G>A(p.r369 h).Conclusion In Children’s Hospital Affiliated to Zhengzhou University,MMA combined with homocysteinemia is the most common type,in which the pathogenic gene is MMACHC.Mutation c.609 G>A(p.W203 X)and c.80 A>G(p.Q27 R)may be the hot spot mutations in Henan.More cases are diagnosed through newborn screening.While their prognosis is relatively better,most clinically diagnosed patients suffer from psychomotor retardation.