1. New Insights into Gastrointestinal Involvement in Late-Onset Pompe Disease: Lessons Learned from Bench and Bedside
- Author
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Kanecia O. Zimmerman, Aditi Korlimarla, Priya S. Kishnani, Paul McIntosh, Baodong Sun, and Jeong-A Lim
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Pediatrics ,Late onset ,Disease ,Article ,late-onset Pompe disease ,03 medical and health sciences ,0302 clinical medicine ,gastrointestinal ,smooth muscles ,PROMIS–GI symptom scales ,GAAKO mice ,glycogen storage disorder ,translational research ,patient-reported outcomes measures ,medicine ,Medical history ,In patient ,Alglucosidase alfa ,Disease burden ,business.industry ,General Medicine ,Enzyme replacement therapy ,030104 developmental biology ,Medicine ,Histopathology ,business ,030217 neurology & neurosurgery ,medicine.drug - 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 6neo/6neo). 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.
- Published
- 2021