Nighttime breathing issues can emerge even with early Pompe care

People with infantile-onset Pompe disease (IOPD) may develop breathing issues during nighttime sleep even if they start enzyme replacement therapy (ERT) very early in life and don’t show obvious declines in daytime respiratory function or motor abilities, a long-term study in Taiwan suggested.

Researchers who followed 16 people with IOPD for nearly two decades found that 11 developed clinically relevant sleep apnea, typically during childhood, despite ERT starting at a median age of under one month. Sleep apnea causes breathing to repeatedly stop and start during sleep. Seven participants eventually required breathing support while sleeping.

In some, these nighttime breathing problems — detected with overnight sleep studies (polysomnography) — emerged while motor abilities remained good or daytime respiratory function appeared relatively preserved.

“Nocturnal sleep abnormalities can occur in early-treated IOPD patients before frank deterioration of motor and respiratory function,” the researchers wrote. “Polysomnography is recommended for all those patients, and night-time respiratory support may be necessary to prevent morbidity and mortality.”

The study, “Nocturnal sleep abnormalities occur before motor function deterioration in early-treated patients with infantile-onset Pompe disease: a two-decade newborn screening cohort study,” was published in Neuromuscular Disorders.

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Pompe is marked by progressive muscle weakness due to the harmful buildup of the complex sugar glycogen in muscle cells. In classic IOPD, the most severe Pompe type, symptoms, including heart and breathing problems, typically appear during the first months of life. Nonclassic IOPD also begins during infancy but is generally less severe and progresses more slowly.

Newborn screening can identify IOPD before Pompe symptoms become apparent. This allows ERT — the standard treatment for Pompe — to begin within the first days or weeks of life, helping prevent irreversible heart damage and significantly improving survival.

Breathing problems can persist or emerge despite treatment, particularly during sleep, and regular sleep studies using polysomnography are recommended even for people who appear stable.

However, much of the evidence behind these recommendations comes from people who began treatment after symptoms appeared, leaving the long-term respiratory outcomes of people treated from early infancy unclear.

A team of researchers in Taiwan followed 16 people with IOPD who started ERT early in infancy at a specialized center. Thirteen of them had classic IOPD, and three had nonclassic IOPD. ERT was started at a median age of 0.8 months, or about three weeks. At the end of follow-up, participants had reached a median age of 16.

Daytime respiratory function was assessed using forced vital capacity (FVC), which measures how much air a person can forcibly breathe out after a deep breath. FVC was measured both while sitting and lying down in participants older than 5.

The researchers used overnight polysomnography to assess breathing during sleep, using measures including the apnea-hypopnea index (AHI), which quantifies how often breathing stops per hour of sleep. They also tracked participants’ motor abilities.

Over time, 11 of the 16 participants developed an AHI above five events per hour, the threshold used by the researchers to indicate moderate obstructive sleep apnea. Nearly all of these events were obstructive apneas or hypopneas, meaning the airway became blocked or narrowed, causing breathing to stop or decrease during sleep.

The estimated median age at which participants first crossed that threshold was 7.8, indicating that sleep apnea could emerge during childhood despite ERT starting in infancy.

Seven participants eventually required noninvasive breathing support while sleeping because of severe obstructive sleep apnea. Support was started at a median age of 17.5, though starting ages ranged from 5 to 18.5.

Nighttime breathing problems tended to worsen faster in participants who eventually lost the ability to walk. In some participants, however, significant sleep apnea developed despite relatively preserved gross motor abilities, such as the ability to walk, or daytime respiratory function.

Overall, AHI tended to increase as FVC declined, but the relationship was modest, suggesting that daytime respiratory tests alone may not always reveal breathing problems that occur during sleep.

This pattern may partly reflect how Pompe affects the breathing muscles. During the day, accessory breathing muscles can help compensate for weakness of the diaphragm, the main muscle used for breathing. When sleeping lying down, however, the diaphragm may be compressed by internal organs, making breathing problems more apparent. Airway and nervous system abnormalities may also contribute.

“Early-treated IOPD patients were susceptible to respiratory problems, especially nocturnal respiratory abnormalities,” the researchers wrote. “Because even a good motor function or acceptable daytime respiratory function does not exclude the risk of sleep apnea, polysomnography should be periodically monitored for these patients especially passing five years of age.”