New Insights into Gastrointestinal Involvement in Late-Onset Pompe Disease: Lessons Learned from Bench and Bedside

Aditi Korlimarla; Jeong-A Lim; Paul McIntosh; Kanecia Zimmerman; Baodong D Sun; Priya S Kishnani

doi:10.3390/jcm10153395

New Insights into Gastrointestinal Involvement in Late-Onset Pompe Disease: Lessons Learned from Bench and Bedside

J Clin Med. 2021 Jul 30;10(15):3395. doi: 10.3390/jcm10153395.

Authors

Aditi Korlimarla¹, Jeong-A Lim¹, Paul McIntosh², Kanecia Zimmerman³, Baodong D Sun¹, Priya S Kishnani¹

Affiliations

¹ Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA.
² Department of Neurology, Duke University Medical Center, Durham, NC 27710, USA.
³ Duke Clinical Research Institute, Durham, NC 27710, USA.

Abstract

Background: There are new emerging phenotypes in Pompe disease, and studies on smooth muscle pathology are limited. Gastrointestinal (GI) manifestations are poorly understood and underreported in Pompe disease.

Methods: To understand the extent and the effects of enzyme replacement therapy (ERT; alglucosidase alfa) in Pompe disease, we studied the histopathology (entire GI tract) in Pompe mice (GAAKO 6^neo/6^neo). To determine the disease burden in patients with late-onset Pompe disease (LOPD), we used Patient-Reported Outcomes Measurements Information System (PROMIS)-GI symptom scales and a GI-focused medical history.

Results: Pompe mice showed early, extensive, and progressive glycogen accumulation throughout the GI tract. Long-term ERT (6 months) was more effective to clear the glycogen accumulation than short-term ERT (5 weeks). GI manifestations were highly prevalent and severe, presented early in life, and were not fully amenable to ERT in patients with LOPD (n = 58; age range: 18-79 years, median age: 51.55 years; 35 females; 53 on ERT).

Conclusion: GI manifestations cause a significant disease burden on adults with LOPD, and should be evaluated during routine clinical visits, using quantitative tools (PROMIS-GI measures). The study also highlights the need for next generation therapies for Pompe disease that target the smooth muscles.

Keywords: GAAKO mice; PROMIS–GI symptom scales; gastrointestinal; glycogen storage disorder; late-onset Pompe disease; patient-reported outcomes measures; smooth muscles; translational research.