Untargeted metabolomic profiling in a patient with glycogen storage disease Ib receiving empagliflozin treatment.

Glycogen storage disease type Ib (GSD-Ib) is a rare inborn error of glycogen metabolism uniquely associated with neutropenia and neutrophil dysfunction, causing severe infections, inflammatory bowel disease (IBD), and impaired wound healing. Recently, kidney sodium-glucose co-transporter-2 (SGLT2) inhibitors such as empagliflozin known to reduce plasma levels of 1,5-anhydroglucitol (1,5-AG) and its toxic derivatives in neutrophils, have been described as a new treatment option in case reports of patients with GSD-Ib from Europe and Asia. We report our experience with an 11-year-old girl with GSD-Ib presenting with short fasting hypoglycemia, neutropenia with neutrophil dysfunction, recurrent infections, suboptimal growth, iron-deficiency anemia, and IBD. Treatment with daily empagliflozin improved neutrophil counts and function with a significant reduction in G-CSF needs. Significant improvement in IBD has led to weight gain with improved nutritional markers and improved fasting tolerance. Reduction of maximum empagliflozin dose was needed due to arthralgia. No other significant side effects of empagliflozin were observed. This report uniquely highlights the novel use of untargeted metabolomics profiling for monitoring plasma levels of 1,5-AG to assess empagliflozin dose responsiveness and guide dietary management and G-CSF therapy. Clinical improvement correlated to rapid normalization of 1,5-AG levels in plasma sustained after dose reduction. In conclusion, empagliflozin appeared to be a safe treatment option for GSD-Ib-associated neutropenia and neutrophil dysfunction. Global untargeted metabolomics is an efficient method to assess biochemical responsiveness to treatment.