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

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.

Duke Scholars

Author Kanecia Obie Zimmerman Pediatrics, Critical Care Medicine

Author Baodong Sun Pediatrics, Medical Genetics

Author Priya Sunil Kishnani Pediatrics, Medical Genetics