Clinical characteristics, gene mutations and enzyme replacement therapy of 13 children with Pompe disease / 中华实用儿科临床杂志

ABSTRACT

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.