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eP034: Novel use of global untargeted metabolomics in a patient with glycogen storage disease Ib receiving off label empagliflozin treatment

      Background

      Glycogen storage disease type Ib (GSD-Ib) is a rare inborn error of glycogen metabolism. Affected individuals present with fasting intolerance, severe hypoglycemia, hepatomegaly, and lactic acidosis. The disorder is uniquely associated with neutropenia and neutrophil dysfunction causing serious infections, inflammatory bowel disease (IBD), mucosal lesions, 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.

      Case presentation

      We hereby 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, recurrent abdominal pain, and loose stools. Treatment with daily empagliflozin resulted in improvement in neutrophil counts and function, leading to resolution of recurrent infections and mouth sores with significant reduction in G-CSF needs. Significant improvement in IBD symptoms with normalization of inflammatory markers and bowel imaging has led to weight gain with improved nutritional markers. Furthermore, improvement of IBD symptoms allowed spacing of meals and cornstarch doses and improved fasting intolerance. Reduction of maximum empagliflozin dose was needed due to arthralgia. No other significant side effects of empagliflozin were observed, including hypoglycemia. This report also highlights novel use of global metabolomics for monitoring plasma levels of 1,5-anhydroglucitol to assess empagliflozin dose responsiveness and guide dietary management as well as G-CSF therapy. Clinical improvement correlated to rapid normalization of 1,5-AG levels in plasma that was sustained after dose reduction.

      Conclusion

      SGLT2 inhibitors are a new and safe treatment option for GSD-Ib-associated neutropenia and neutrophil dysfunction leading to overall improvement in other manifestations of the disease. Global untargeted metabolomics is an efficient method to assess biochemical responsiveness to treatment.