Introduction: Neutropenia and neutrophil dysfunction are unique manifestations of Glycogen storage disease type 1B (GSD 1B). Treatment with granulocyte colony-stimulating factor (G-CSF) increases neutrophil count and improves symptoms of enterocolitis, although not correcting neutrophils function.
A recent discovery that accumulation of 1,5AG6P, a glucose analogue, in neutrophils causes neutropenia and neutrophils dysfunction in GSD 1B, led to off-label use of Empagliflozin, SGLT2 inhibitor, in patients with GSD1B. Empaglyflozin reduces 1,5AG6P in neutrophils, subsequently leading to symptom resolution. These encouraging results led us to commence off-label treatment with Empagliflozin in a 14-year-old boy with GSD 1B and severe neutrophil-dysfunction associated symptoms.
Case presentation: Patient was diagnosed with GSD 1B shortly after birth due to hypoglycemia and a family history. Severe enterocolitis developed while on G-CSF treatment. Treatment with G-CSF, elemental diet, systemic glucocorticoids and 5-aminosalicylic acid did not yield satisfactory response. He was dependent on red-blood-cell transfusions due to severe red-cell aplasia. Neutrophil function tests before treatment with Empaglyflozin were grossly abnormal, with complete normalization on repeated testing following two weeks of treatment. Steroids were stopped for the first time in years. Currently, he does not have any active IBD-like signs or symptoms. He has not require red-blood-cell transfusion for the last few months. Repeated bone marrow aspiration and biopsy demonstrated recovery of red cell lineage.
Conclusion: Understanding the underlying mechanism of neutropenia and neutrophil dysfunction in GSD 1B has led to repurposing use of Empaglyflozin with promising results, opening a new era in treating this debilitating disease.