{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T14:37:56Z","timestamp":1790087876460,"version":"4.0.1"},"reference-count":42,"publisher":"American Society of Hematology","issue":"9","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,8,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Neutropenia and neutrophil dysfunction cause serious infections and inflammatory bowel disease in glycogen storage disease type Ib (GSD-Ib). Our discovery that accumulating 1,5-anhydroglucitol-6-phosphate (1,5AG6P) caused neutropenia in a glucose-6-phosphatase 3 (G6PC3)\u2013deficient mouse model and in 2 rare diseases (GSD-Ib and G6PC3 deficiency) led us to repurpose the widely used antidiabetic drug empagliflozin, an inhibitor of the renal glucose cotransporter sodium glucose cotransporter 2 (SGLT2). Off-label use of empagliflozin in 4 GSD-Ib patients with incomplete response to granulocyte colony-stimulating factor (GCSF) treatment decreased serum 1,5AG and neutrophil 1,5AG6P levels within 1 month. Clinically, symptoms of frequent infections, mucosal lesions, and inflammatory bowel disease resolved, and no symptomatic hypoglycemia was observed. GCSF could be discontinued in 2 patients and tapered by 57% and 81%, respectively, in the other 2. The fluctuating neutrophil numbers in all patients were increased and stabilized. We further demonstrated improved neutrophil function: normal oxidative burst (in 3 of 3 patients tested), corrected protein glycosylation (2 of 2), and normal neutrophil chemotaxis (1 of 1), and bactericidal activity (1 of 1) under treatment. In summary, the glucose-lowering SGLT2 inhibitor empagliflozin, used for type 2 diabetes, was successfully repurposed for treating neutropenia and neutrophil dysfunction in the rare inherited metabolic disorder GSD-Ib without causing symptomatic hypoglycemia. We ascribe this to an improvement in neutrophil function resulting from the reduction of the intracellular concentration of 1,5AG6P.<\/jats:p>","DOI":"10.1182\/blood.2019004465","type":"journal-article","created":{"date-parts":[[2020,4,15]],"date-time":"2020-04-15T18:34:22Z","timestamp":1586975662000},"page":"1033-1043","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":139,"title":["Treating neutropenia and neutrophil dysfunction in glycogen storage disease type Ib with an SGLT2 inhibitor"],"prefix":"10.1182","volume":"136","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1968-8103","authenticated-orcid":false,"given":"Saskia B.","family":"Wortmann","sequence":"first","affiliation":[{"name":"University Children\u2019s Hospital, Paracelsus Medical University (PMU), Salzburg, Austria;"},{"name":"Institute of Human Genetics, Technical University M\u00fcnchen, Munich, Germany;"},{"name":"Radboud Center for Mitochondrial Medicine, Department of Pediatrics, Amalia Children\u2019s Hospital, Radboud University Medical Center, Nijmegen, The Netherlands;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan L. 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