摘要
目的总结儿童庞贝病(PD)的临床特点、基因突变及酶替代治疗(ERT)经验。方法回顾性分析2016年12月至2021年8月青岛市妇女儿童医院收治的PD患儿临床资料, 根据发病年龄将患儿分为婴儿型庞贝病(IOPD)组和晚发型庞贝病(LOPD)组, 根据是否予静脉输注人重组酸性α-葡萄糖苷酶(rhGAA)分为ERT组和无ERT组, ERT组根据是否规范应用rhGAA分为规范ERT组[规范应用rhGAA为间隔时间约2周, 剂量为20 mg/(kg·次), 共持续52周]和未规范ERT组。采用Kaplan-Meier法对组间生存率进行比较。结果 13例PD患儿中, 男7例, 女6例;IOPD 10例, LOPD 3例;前者的首诊原因以心脏受累者最多[6例(60.0%)], 后者的首诊原因分别为肌无力、心脏受累和呼吸道感染。患儿肌酸激酶均不同程度升高;1例酸性α-葡糖苷酶(GAA)活性完全缺乏, 12例活性降低。IOPD患儿均有心肌肥厚, 十二导联心电图示短PR间期、高大QRS波和广泛T波倒置。GAA基因分析共发现c.1861T>G(p.Trp621Gly)、c.2278A>T(p.K760X)和c.949G>A(p.A317T)3个新发突变位点。IOPD组10例中, 5例患儿给予ERT, 其中2例规范治疗52周, 3例为未规范治疗;2例规范ERT者存活, 余8例死于心力衰竭或呼吸衰竭。LOPD组中仅1例给予ERT 1次, 其中2例存活, 1例死于呼吸衰竭。总病死率为69.2%(9/13例)。ERT组患儿(50.0%)及规范ERT组患儿(100.0%)的生存率均高于无ERT组患儿(14.3%)(Log Rank P=0.037、0.044)。结论 PD临床表现具有多样性, GAA酶活性测定及GAA基因分析是临床诊断的重要手段;规范且早期ERT可延缓病情进展, 甚至可逆转IOPD患儿的心肌肥厚。
Objective To summarize the clinical features,gene mutations and experience of standardized enzyme replacement therapy(ERT)of Pompe disease(PD)in children.Methods A retrospective analysis was performed on the clinical data of 13 children with PD,who were hospitalized in Qingdao Women and Children′s Hospital from December 2016 to August 2021.According to the age at onset,the children were divided into the infantile-onset Pompe disease(IOPD)group and late-onset Pompe disease(LOPD)group.At the same time,they were divided into the ERT group and non-ERT group according to whether recombinant human acid alpha-glucosidase(rhGAA)was infused.Furthermore,the ERT group was divided into the standard ERT group and non-standard ERT group.The standard ERT group received a dose of 20 mg/kg every 2 weeks for 52 weeks.The survival rate was compared between groups by using the Kaplan-Meier method.Results Among the 13 children with PD,there were 7 males and 6 females.Ten cases belonged to the IOPD group and 3 cases belonged to the LOPD group.The most common cause of initial consultation in the IOPD group was cardiac involvement,which accounted for 60.0%(6/10 cases),while the LOPD group mainly presented with myasthenia,cardiac involvement and respiratory tract infection at the first diagnosis.The serum level of creatine kinase(CK)in all cases increased to varying degrees.Acid alpha-glucosidase(GAA)was completely deficient in 1 case and decreased in 12 cases.All the children in the IOPD group showed myocardial hypertrophy,electrocardiograph(ECG)suggested a short PR interval,increased QRS voltage and extensive T-wave inversion.Three new mutations were found by GAA gene analysis,and they were c.1861T>G(p.Trp621Gly),c.2278A>T(p.K760X),and c.949G>A(p.A317T).Five cases in the IOPD group were given ERT.Two of them were given standard ERT for 52 weeks,and the other 3 cases were treated with non-standard ERT.At the end of follow-up,2 cases treated with standardized ERT survived and the remaining 8 cases died of heart failure or respiratory failure.In the LOPD group,only 1 case was given ERT one time.Finally,2 cases survived and one died of respiratory failure.The total fatality rate was 69.2%(9/13 cases).The survival rate of the ERT group(50.0%)and standard ERT group(100.0%)was significantly higher than that of the non-ERT group(14.3%)(Log Rank P=0.037,0.044).Conclusions The clinical manifestations of PD are diverse.GAA activity examination and GAA gene analysis are important for clinical diagnosis of PD.Standardized ERT can significantly delay the progression of PD and even reverse myocardial hypertrophy in children with IOPD.
作者
轩欢欢
王本臻
单光颂
申金梅
邴振
纪志娴
李自普
Xuan Huanhuan;Wang Benzhen;Shan Guangsong;Shen Jinmei;Bing Zhen;Ji Zhixian;Li Zipu(Heart Center,Qingdao Women and Children′s Hospital,Qingdao 266034,China;Pediatric Intensive Care Unit,Qingdao Women and Children′s Hospital,Qingdao 266034,China)
出处
《中华实用儿科临床杂志》
CAS
CSCD
北大核心
2022年第18期1392-1397,共6页
Chinese Journal of Applied Clinical Pediatrics
基金
青岛市医疗卫生优秀人才培养项目(青卫科教字(2017)9号)。
关键词
庞贝病
临床特点
基因分析
酶替代治疗
儿童
Pompe disease
Clinical feature
Gene analysis
Enzyme replacement therapy
Child
