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Lowering blood 1,5\u2010AG with an SGLT2 inhibitor greatly improved neutrophil counts and function in G6PC3\u2010deficient mice and in patients with G6PT\u2010deficiency. We evaluate this treatment in two G6PC3\u2010deficient children. While neutropenia was severe in one child (PT1), which was dependent on granulocyte cololony\u2010stimulating factor (GCSF), it was significantly milder in the other one (PT2), which had low blood 1,5\u2010AG levels and only required GCSF during severe infections. Treatment with the SGLT2\u2010inhibitor empagliflozin decreased 1,5\u2010AG in blood and 1,5\u2010AG6P in neutrophils and improved (PT1) or normalized (PT2) neutrophil counts, allowing to stop GCSF. On empagliflozin, both children remained infection\u2010free (&gt;1\u00a0year \u2013 PT2; &gt;2\u2009years \u2013 PT1) and no side effects were reported. Remarkably, sequencing of SGLT5, the gene encoding the putative renal transporter for 1,5\u2010AG, disclosed a rare heterozygous missense mutation in PT2, replacing the extremely conserved Arg401 by a histidine. The higher urinary clearance of 1,5\u2010AG explains the more benign neutropenia and the outstanding response to empagliflozin treatment found in this child. Our data shows that SGLT2 inhibitors are an excellent alternative to treat the neutropenia present in G6PC3\u2010deficiency.<\/jats:p>","DOI":"10.1002\/jimd.12509","type":"journal-article","created":{"date-parts":[[2022,5,4]],"date-time":"2022-05-04T05:41:10Z","timestamp":1651642870000},"page":"759-768","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Successful use of empagliflozin to treat neutropenia in two\n                    <scp>G6PC3<\/scp>\n                    \u2010deficient children: Impact of a mutation in\n                    <scp>SGLT5<\/scp>"],"prefix":"10.1002","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2969-6131","authenticated-orcid":false,"given":"C\u00e9cile","family":"Boulanger","sequence":"first","affiliation":[{"name":"Biologie H\u00e9matologique Cliniques Universitaires Saint\u2010Luc, UCLouvain  Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1381-2265","authenticated-orcid":false,"given":"Xavier","family":"Stephenne","sequence":"additional","affiliation":[{"name":"Service de Gastro\u2010Ent\u00e9rologie et H\u00e9patologie P\u00e9diatrique Cliniques Universitaires Saint\u2010Luc, UCLouvain  Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Diederich","sequence":"additional","affiliation":[{"name":"Groupe de Recherches Metaboliques de Duve Institute, UCLouvain  Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Mounkoro","sequence":"additional","affiliation":[{"name":"Groupe de Recherches Metaboliques de Duve Institute, UCLouvain  Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Chevalier","sequence":"additional","affiliation":[{"name":"Groupe de Recherches Metaboliques de Duve Institute, UCLouvain  Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9920-8359","authenticated-orcid":false,"given":"Alina","family":"Ferster","sequence":"additional","affiliation":[{"name":"Department of Hematology\/Oncology H\u00f4pital Universitaire des Enfants Reine Fabiola, Universit\u00e9 Libre de Bruxelles  Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6199-7647","authenticated-orcid":false,"given":"Emile","family":"Van Schaftingen","sequence":"additional","affiliation":[{"name":"Groupe de Recherches Metaboliques de Duve Institute, UCLouvain  Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2968-7374","authenticated-orcid":false,"given":"Maria","family":"Veiga\u2010da\u2010Cunha","sequence":"additional","affiliation":[{"name":"Groupe de Recherches Metaboliques de Duve Institute, UCLouvain  Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,5,24]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0805051"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1086\/302068"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1816143116"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-12210-z"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2019004465"},{"issue":"2","key":"e_1_2_9_7_1","first-page":"E268","article-title":"Origin and disposal of 1,5\u2010anhydroglucitol, a major polyol in the human body","volume":"263","author":"Yamanouchi T","year":"1992","journal-title":"Am J 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