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

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

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

dc.contributor.author	Korlimarla, Aditi
dc.contributor.author	Lim, Jeong-A
dc.contributor.author	McIntosh, Paul
dc.contributor.author	Zimmerman, Kanecia
dc.contributor.author	Sun, Baodong D
dc.contributor.author	Kishnani, Priya S
dc.date.accessioned	2021-12-01T14:48:30Z
dc.date.available	2021-12-01T14:48:30Z
dc.date.issued	2021-07-30
dc.date.updated	2021-12-01T14:48:25Z
dc.description.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.
dc.identifier	jcm10153395
dc.identifier.issn	2077-0383
dc.identifier.issn	2077-0383
dc.identifier.uri	https://hdl.handle.net/10161/24021
dc.language	eng
dc.publisher	MDPI AG
dc.relation.ispartof	Journal of clinical medicine
dc.relation.isversionof	10.3390/jcm10153395
dc.subject	GAAKO mice
dc.subject	PROMIS–GI symptom scales
dc.subject	gastrointestinal
dc.subject	glycogen storage disorder
dc.subject	late-onset Pompe disease
dc.subject	patient-reported outcomes measures
dc.subject	smooth muscles
dc.subject	translational research
dc.title	New Insights into Gastrointestinal Involvement in Late-Onset Pompe Disease: Lessons Learned from Bench and Bedside.
dc.type	Journal article
duke.contributor.orcid	Korlimarla, Aditi\|0000-0002-0680-9949
duke.contributor.orcid	Zimmerman, Kanecia\|0000-0003-3748-6932
duke.contributor.orcid	Sun, Baodong D\|0000-0002-2191-0025
duke.contributor.orcid	Kishnani, Priya S\|0000-0001-8251-909X
pubs.begin-page	3395
pubs.end-page	3395
pubs.issue	15
pubs.organisational-group	School of Medicine
pubs.organisational-group	Pediatrics, Medical Genetics
pubs.organisational-group	Duke
pubs.organisational-group	Pediatrics
pubs.organisational-group	Clinical Science Departments
pubs.organisational-group	Duke Clinical Research Institute
pubs.organisational-group	Pediatrics, Critical Care Medicine
pubs.organisational-group	Institutes and Centers
pubs.publication-status	Published
pubs.volume	10