丙酸血症患儿82例治疗及随访分析  

Treatment and follow-up of 82 children with propionic acidemia

作　　者：胡宇慧[1] 韩连书[2] 叶军[2] 邱文娟[2] 张惠文[2] 梁黎黎[2] 季文君[2] 徐烽[2] 陈婷[2] 陈淑丽[1] 顾学范[2] Hu Yuhui;Han Lianshu;Ye Jun;Qiu Wenjuan;Zhang Huiwen;Liang Lili;Ji Wenjun;Xu Feng;Chen Ting;Chen Shuli;Gu Xuefan(Department of Genetic Metabolism,Shenzhen City Children's Hospital,Shenzhen 518026,China;Department of Pediatric Endocrinology and Genetics,Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine,Shanghai Institute for Pediatric Research,Shanghai 200092,China)

机构地区：[1]深圳市儿童医院遗传代谢病科,518026 [2]上海交通大学医学院附属新华医院上海市儿科医学研究所小儿内分泌遗传代谢科,200092

出　　处：《中华围产医学杂志》2021年第2期105-112,共8页Chinese Journal of Perinatal Medicine

基　　金：国家重点研发计划 (2016YFC0901505)。

摘　　要：目的了解丙酸血症患儿的治疗现状和预后。方法对2002年12月至2020年6月上海交通大学医学院附属新华医院小儿内分泌遗传代谢科诊治的82例丙酸血症患儿临床表现、实验室检测结果、治疗措施及随访情况进行总结和分析。采用t检验或Mann-Whitney U检验对数据进行统计学分析。结果(1)82例患儿中,男50例(61.0%),女32例(39.0%);59例(72.0%)为临床发病后确诊;22例(26.8%)为新生儿筛查确诊,其中8例未发病;1例(1.2%)为同胞确诊后完善相关检查确诊,但未发病。73例临床发病患儿初次发病年龄为4.5个月(2 d~5岁),其中28例(38.4%)为早发型(≤3月龄发病)。(2)共26例进行了MRI检查,其中19例(73.1%)存在异常影像学表现。(3)53.3%(16/30)患儿乳酸升高,水平为3.5(2.1~4.3)μmol/L;87.5%(35/40)患儿血氨升高,水平为105.4(34~907)μmol/L。(4)28例早发型患儿中,16例(57.1%)死亡,12例(42.9%)存活。存活与死亡患儿血丙酰肉碱水平、丙酰肉碱与乙酰肉碱比值,以及尿3-羟基丙酸和甲基枸橼酸水平差异无统计学意义。(5)75例(91.5%)患儿检测到基因突变,其中34.7%(26/75)检测到PCCA基因突变,64%(48/75)检测到PCCB基因突变;1例(1.3%)在PCCA和PCCB各检测到1种已报道致病突变,所有突变均来源于父母。(6)随访至2020年6月,82例患儿中,57例(69.5%)患儿存活,25例(30.5%)死亡。死亡患儿均为严重酸中毒导致多器官功能衰竭,其中16例为早发型,9例为晚发型。结论丙酸血症患儿多在临床发病后确诊,治疗方法以饮食控制为主。经治疗,部分新生儿筛查确诊的患儿未发病,但部分发病后确诊的患儿仍有发病,可能出现发育落后。建议积极开展新生儿串联质谱筛查,以早期诊断和治疗。Objective To investigate the treatment and prognosis of children with propionic acidemia(PA).Methods This study involved 82 children with PA treated in the Department of Pediatric Endocrinol-ogy and Genetic Metabolism,Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine from December 2002 to June 2020.Clinical data,including manifestations,laboratory test results,treatment strategy,and follow-up data,were summarized and analyzed using t-test or Mann-Whitney U test.Results(1)Among the 82 cases consisting of 50(61.0%)boys and 32(39.0%)girls,59(72.0%)were diagnosed after clinical onset;22(26.8%)were diagnosed by newborn screening,including eight asymptomatic ones;the other one(1.2%)was asymptomatic but confirmed after the diagnosis of PA in the patient's sibling.The average age at first onset was 4.5 months(2 d-5 years)in 73 subjects,of which 28(38.4%)were early-onset PA(within three months after birth).(2)Cranial MRI was performed on 26 cases,and abnormality was identified in 19(73.1%)cases.(3)Hyperlactatemia was found in 16 cases among 30(53.3%)who underwent relevant examination with the average lactic acid level of 3.5(2.1-4.3)μmol/L,while 35 out of 40 patients(87.5%)had hyperammonemia with an average blood ammonia level of 105.4(34-907)μmol/L.(4)Among the 28 early-onset PA cases,16(57.1%)died,and 12(42.9%)survived.There was no significant difference in the serum propionylcarnitine level,propionylcarnitine to acetylcarnitine ratio,urine 3-hydroxypropionic acid,or methylcitrate level between the survival and death cases.(5)Genetic mutations were detected in 75 patients(91.5%),among which 26(34.7%)carried PCCA gene mutations and 48(64%)with PCCB gene mutations.One patient(1.3%)harbored one known pathogenic mutation in each of the PCCA and PCCB genes.All mutations were inherited from the parents.(6)Followed up to June 2020,57(69.5%)patients survived,and 25(30.5%)died from multiple organ failure secondary to severe acidosis,including 16 early-onset and nine late-onset cases.Conclusions The

关 键 词：丙酸血症 串联质谱法 气相色谱质谱 治疗 随访 

分 类 号：R725.9[医药卫生—儿科]