Background: A high prevalence of infantile-onset Pompe disease (IOPD) in the Chinese population has been noted, but there are currently no reported clinical trials of enzyme replacement therapy (ERT) for IOPD in this population. The purpose of this study was to evaluate the efficacy and safety of alglucosidase alfa in Chinese patients with IOPD.Materials and Methods: A multicentre, single-arm, prospective, open-label clinical trial was performed at 4 sites in China. Eligible Chinese subjects with IOPD received an infusion of alglucosidase alfa at a dose of 20 mg/kg every 2 weeks for up to 52 weeks. The primary endpoints of clinical efficacy were the survival rate and changes in the left ventricular mass index (LVMI). The safety assessment was based on the incidence of adverse events (AEs).Results: A total of 10 eligible subjects were enrolled in the study. The mean age at the start of ERT was 5.36 ± 1.56 months. Nine subjects had survived after 52 weeks of treatment. One subject discontinued the study and died after mechanical ventilation was withdrawn. The intent-to-treat analysis demonstrated that the survival rate was 90.0% (95% confidence interval: 55.5–99.7%). The mean LVMI at week 52 was 70.59 ± 39.93 g/m2 compared to that of 298.02 ± 178.43 g/m2 at baseline, with a difference of -227.60 ± 155.99 g/m2. All subjects had left ventricular mass (LVM) Z scores >10 at baseline, and eight subjects (80%) achieved Z scores <5 at week 52. No treatment-related AEs were observed, and no AEs led to the discontinuation of treatment.Conclusions: This clinical trial is the first study of ERT for IOPD in China, indicating that alglucosidase alfa has favourable efficacy and safety for the treatment of Chinese patients with IOPD (ClinicalTrials.gov number, NCT03687333).

Sengers syndrome (OMIM #212350) is a rare autosomal recessive disorder due to mutations in acylglycerol kinase (AGK) gene. We report two cases that were diagnosed clinically and confirmed genetically. Both infants had typical clinical features characterized by hypertrophic cardiomyopathy, bilateral cataracts, myopathy, and lactic acidosis, and heart failure was the most severe manifestation. Genetic testing of a boy revealed a homozygous pathogenic variant for Sengers syndrome in AGK (c.1131+2T>C) which was classified as likely pathogenic according to the ACMG guideline; besides, his skeletal muscle biopsy and transmission electron microscope presented obvious abnormity. One girl had compound heterozygous (c.409C>T and c.390G>A) variants of AGK gene that was identified in the proband and further Sanger sequencing indicated that the parents carried a single heterozygous mutation each. After the administration of “cocktail” therapy including coenzyme Q10, carnitine, and vitamin B complex, as well as ACEI, heart failure and myopathy of the boy were significantly improved and the condition was stable after 1-year follow-up, while the cardiomyopathy of the girl is not progressive but the plasma lactate acid increased significantly. We present the first report of two infants with Sengers syndrome diagnosed via exome sequencing in China.

Dilated cardiomyopathy (DCM) is one of the leading causes of heart failure in children with diverse clinical characteristics. To date, DCM with a giant atrium as the first manifestation is rare and has not been reported in previous literature. We report a case of a male infant born with a significantly enlarged right atrium. Due to worsened clinical symptoms and the risk of arrhythmias and thrombosis, we performed the surgical reduction of the right atrium. Unfortunately, DCM and a progressive re-enlargement of the right atrium appeared during midterm follow-up. The mother's echocardiogram also suggested DCM, and the patient was eventually considered for a diagnosis of familial DCM. This case may expand the clinical spectrum of DCM and reminds us of the importance of good follow-up of children with idiopathic dilatation of the right atrium.