[Clinical and genetic characteristics of infantile-onset Pompe disease​ and long-term efficacy of enzyme replacement therapy].

Objective

To analyze the clinical and genetic characteristics of infantile-onset Pompe disease (IOPD) and evaluate the long-term efficacy of enzyme replacement therapy (ERT).

Methods

A retrospective cohort study was conducted on 24 IOPD patients diagnosed and treated at the Children's Hospital, Zhejiang University School of Medicine, between December 2016 and June 2025. Clinical and genetic variation characteristics of patients were analyzed. According to the whether received alglucosidase α and gene therapy, patients were stratified into ERT group, non-ERT group and gene therapy group. Baseline characteristics, including gender, weight, age at symptom onset and diagnosis, degree of cardiac hypertrophy and gene coding for acid alpha-glucosidase (GAA)enzyme activity were compared among the three groups using Fisher exact test or the Kruskal-Wallis H test, as appropriate. Within the ERT group, Friedman test followed by Wilcoxon signed-rank tests were used to compare efficacy before treatment at 12 and 36 months of treatment. Kaplan-Meier method was performed for survival analysis.

Results

Among the 24 patients, there were 13 males (54%) and 11 females (46%). The age of onset and diagnosis was 1.8 (0.9,3.0) and 4.8 (2.7,6.7) months, respectively. Significant differences were found among the ERT, no-ERT, and gene therapy groups in gender distribution and body weight (all P<0.05). However, no statistically significant differences were observed in age at onset, age at diagnosis, presence of muscle weakness, feeding difficulties, heart failure, degree of cardiac hypertrophy or GAA enzyme activity (all P>0.05). After 12 months of ERT, significant reductions were observed in interventricular septal thickness, left ventricular posterior wall thickness and left ventricular mass index (LVMI) (all P<0.05).​​ Serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels showed significant differences at both the 12 and 36-month follow-up (P<0.05), whereas creatine kinase levels did not change significantly at these time points (P>0.05). Among the 5 patients in ERT group followed for 36 months, 4 patients achieved new motor developmental milestones, while 1 patient showed no significant motor improvement. Survival analysis revealed that all 8 patients in gene therapy group survived, 6 deaths in non-ERT group,and only 1 death in ERT group. The comparison of survival curves between ERT group and non-ERT group showed statistically significant difference (P=0.001). Univariable Firth Cox proportional hazards regression analysis demonstrated that ERT significantly decreased mortality risk (HR=0.04,95%CI 0.00-0.34,P=0.001). Regarding safety, only 1 mild allergic reaction occurred during 468 cumulative infusions in ERT group.

Conclusion

ERT effectively prolongs survival and reverses cardiac hypertrophy in IOPD patients with a favorable safety profile, but its effect on improving skeletal muscle function remains limited.