Gastrointestinal (GI) manifestations cause a significant burden in adults with late-onset Pompe disease, a new study published in the Journal of Clinical Medicine found. They should therefore be evaluated during routine clinical visits, according to the authors of the study.

The results also highlight the need for next-generation therapies for Pompe disease that target the smooth muscles, the researchers wrote.

Gastrointestinal manifestations in Pompe disease are not well studied. To assess the disease’s impact on the GI tract and understand the extent and effects of the enzyme replacement therapy alglucosidase alfa in Pompe disease, a team of researchers led by Priya S. Kishnani, MD, MBBS, studied the histopathology of the entire GI tract in a mouse model of the disease.

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The researchers also assessed disease burden in patients with late-onset Pompe disease using the patient-reported outcomes measurements information system (PROMIS)-GI symptom scales and GI-focused medical histories.

The results showed that Pompe mice displayed early, extensive, and progressive glycogen accumulation throughout the GI tract. This glycogen accumulation was more effectively cleared with long-term enzyme replacement therapy (ie, 6 months), compared to short-term therapy (ie, 5 weeks). 

When the researchers analyzed the answers of 58 patients with late-onset Pompe disease, aged 18 to 79 years, as well as their medical histories, they found that GI manifestations were highly prevalent and severe. About half of the patients had reduced quality of life due to GI symptoms.

In addition, these symptoms usually presented early in life and were not always amenable to enzyme replacement therapy. The currently recommended doses of enzyme replacement therapies seemed futile for maintaining the GI health of patients.

The researchers wrote, “Presumably, an earlier initiation of [enzyme replacement therapy] may mitigate the development and progression of GI symptoms.” They cautioned “however, this could not be concluded from the current study.” 

In the future, second-generation drugs using gene therapy approaches may help to tackle GI problems in patients with late-onset Pompe disease, according to the study authors.


Korlimarla A, Lim JA, McIntosh P, Zimmerman K, Sun BD, Kishnani PS. New insights into gastrointestinal involvement in late-onset Pompe disease: lessons learned from bench and bedside. J Clin Med. 2021;10(15):3395. doi:10.3390/jcm10153395