ERT helps keep breathing stable during sleep in pediatric Pompe disease
Study highlights early treatment access as key to preserving respiratory health
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Children with Pompe disease receiving enzyme replacement therapy (ERT) generally maintained stable breathing during sleep, although some may continue to experience sleep-related respiratory issues requiring ongoing monitoring, a study in France suggests.
Sleep studies showed normal oxygen levels overnight among children with Pompe, while also identifying a small number of patients who needed breathing support or changes to their care.
According to researchers, these findings reinforce that the “identification, ongoing monitoring of [sleep-disordered breathing], and physiological benefits of ERT may mitigate or prevent respiratory [problems].”
The study, “Pediatric sleep-disordered breathing in Pompe disease in the era of enzyme replacement therapy: A retrospective cohort study,” was published in Molecular Genetics and Metabolism.
Sleep-related breathing problems common in Pompe patients
Pompe is caused by mutations in the GAA gene that result in missing or defective acid alpha-glucosidase, an enzyme that helps break down glycogen, the body’s stored form of sugar. As glycogen builds up inside cells — particularly muscle cells — it causes progressive muscle weakness, including weakness of the muscles involved in breathing.
Sleep-related breathing problems are common in people with Pompe and may include obstructive sleep apnea (OSA), in which the airway repeatedly becomes blocked during sleep, and hypoventilation, when breathing becomes too shallow to remove enough carbon dioxide from the body. While ERT has greatly improved survival and other clinical outcomes in Pompe, less is known about its effects on nighttime breathing problems.
To address this knowledge gap, the researchers reviewed sleep studies from 22 children with Pompe disease treated at a specialized center in France between 2017 and 2025.
“Our study is the largest to date to describe [sleep-related] characteristics, along with longitudinal sleep outcome, in a pediatric cohort with Pompe disease treated with ERT at a national reference center,” the team wrote.
Nineteen children had infantile-onset Pompe disease (IOPD) and three had late-onset disease(LOPD). All had been receiving ERT — initially Myozyme (alglucosidase alfa; sold in the U.S. as Lumizyme), and later Nexviadyme (avalglucosidase alfa; Nexviazyme in the U.S.) — for a median of about 3.4 years before their first sleep evaluation. Polysomnography or respiratory polygraphy, which record brain activity, breathing, oxygen levels and heart rate during sleep, were conducted as part of regular clinical follow-up.
Sleep studies helped doctors tailor respiratory care
The first sleep study showed that children had normal oxygen levels throughout the night and generally preserved breathing during sleep.
Children with IOPD experienced a median of 1.6 breathing pauses per hour, with seven (37%) showing mild and one showing moderate OSA.
Those with LOPD experienced a median of 0.6 breathing pauses per hour. One child with LOPD had moderate OSA together with elevated carbon dioxide levels in the blood. Oxygen levels during sleep remained normal in all participants.
The sleep studies also helped doctors tailor respiratory care. Two children with IOPD started long-term noninvasive ventilation (NIV), a form of breathing support, while two others were able to stop using NIV. One child with LOPD continued NIV after the sleep evaluation.
[These findings show] the critical importance of accessibility and initiation of disease-modifying therapy which may prevent or mitigate progression of respiratory status.
Fifteen children underwent additional sleep studies over a median follow-up of three years. Most continued to have normal sleep and breathing patterns. One child who initially required NIV was later able to discontinue after breathing improved, while another continued to need nighttime breathing support.
Overall, these findings show “the critical importance of accessibility and initiation of disease-modifying therapy which may prevent or mitigate progression of respiratory status,” the researchers wrote.
They noted that some children still developed sleep-disordered breathing despite ERT, and they support systematic sleep evaluations to detect those problems, particularly in IOPD children with delayed diagnosis or ERT initiation.
“Future multicenter studies incorporating sleep studies and pulmonary function testing before the initiation of ERT, and genotype-phenotype correlations may refine our understanding of respiratory trajectories and help identify patients most at risk of developing [sleep-related breathing problems] despite ERT,” the team concluded. Genotype-phenotype refers to how genetic mutations are linked to clinical presentation.
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