{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T16:57:41Z","timestamp":1787504261436,"version":"build-2736575974"},"reference-count":110,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T00:00:00Z","timestamp":1757980800000},"content-version":"vor","delay-in-days":15,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100002661","name":"Fonds De La Recherche Scientifique - FNRS","doi-asserted-by":"publisher","award":["T.0239.21"],"award-info":[{"award-number":["T.0239.21"]}],"id":[{"id":"10.13039\/501100002661","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002661","name":"Fonds De La Recherche Scientifique - FNRS","doi-asserted-by":"publisher","award":["J.0231.25"],"award-info":[{"award-number":["J.0231.25"]}],"id":[{"id":"10.13039\/501100002661","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Neutropenia in Glycogen Storage Disease Type Ib (GSDIb) and G6PC3 deficiency results from defects in metabolite repair, leading to the accumulation of 1,5\u2010anhydroglucitol\u20106\u2010phosphate (1,5\u2010AG6P). Treatment currently relies on inhibitors of SGLT2, the renal sodium\u2010glucose co\u2010transporter, which indirectly enhances urinary excretion of 1,5\u2010anhydroglucitol (1,5\u2010AG), the precursor of the toxic 1,5\u2010AG6P that accumulates in neutrophils and is at the origin of these patients' neutropenia. In this context, a detailed understanding of the formation, intestinal absorption, renal reabsorption, and metabolism of 1,5\u2010AG is essential. Here, we review the current knowledge of these mechanisms, their role in the pathophysiology of 1,5\u2010AG6P\u2013related neutropenia, and explore potential strategies to improve treatment outcomes.<\/jats:p>","DOI":"10.1002\/jimd.70085","type":"journal-article","created":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T04:53:42Z","timestamp":1758084822000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Pathophysiology of the Neutropenia of\n                    <scp>GSDIb<\/scp>\n                    and\n                    <scp>G6PC3<\/scp>\n                    Deficiency: Origin, Metabolism and Elimination of 1,5\u2010Anhydroglucitol"],"prefix":"10.1002","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2968-7374","authenticated-orcid":false,"given":"Maria","family":"Veiga\u2010da\u2010Cunha","sequence":"first","affiliation":[{"name":"Metabolic Research Group de Duve Institute and UCLouvain  Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lila","family":"Gannoun","sequence":"additional","affiliation":[{"name":"Metabolic Research Group de Duve Institute and UCLouvain  Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Dewulf","sequence":"additional","affiliation":[{"name":"Biochemical Genetics and Newborn Screening Laboratory, Department of Laboratory Medicine, Cliniques Universitaires Saint\u2010Luc, UCLouvain  Brussels Belgium"},{"name":"Institut des Maladies Rares, Cliniques universitaires Saint\u2010Luc, UCLouvain  Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emile","family":"Van Schaftingen","sequence":"additional","affiliation":[{"name":"Metabolic Research Group de Duve Institute and UCLouvain  Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,16]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.1141"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2019.07.004"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/jimd.12187"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biochi.2005.06.005"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0119540"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-008-1042-3"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2111338119"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1613736114"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-9861(75)90344-6"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1006\/abbi.1998.0939"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C111.310847"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)65307-4"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awy310"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41589-025-01857-9"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41589-025-01852-0"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.09.051"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1816143116"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/jimd.12509"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-023-04884-8"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-019-09640-2"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awac065"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2022.04.003"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmd2.12425"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1086\/427890"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20031933"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-012-9462-5"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-023-02382-9"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-016-9960-y"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.3390\/diagnostics13101803"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2019004465"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/glycob\/cwr023"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2024.108476"},{"key":"e_1_2_12_34_1","first-page":"715","article-title":"Genetics of Glycosylation in Mammalian Development and Disease","volume":"25","author":"Stanley P.","year":"2024","journal-title":"Nature Reviews Genetics"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2017.01.020"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj3620513"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1677\/jme.0.0290205"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R109.025544"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1086\/302068"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0805051"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI30443"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)65384-0"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-09-378117"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-022-04891-w"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1334205"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1098\/rsob.220248"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02072087"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI113457"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-12-258491"},{"key":"e_1_2_12_50_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2023012403"},{"key":"e_1_2_12_51_1","doi-asserted-by":"publisher","DOI":"10.1177\/000992289803700403"},{"key":"e_1_2_12_52_1","doi-asserted-by":"publisher","DOI":"10.1159\/000496181"},{"key":"e_1_2_12_53_1","doi-asserted-by":"publisher","DOI":"10.1111\/omi.12252"},{"key":"e_1_2_12_54_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":"American Journal of Physiology"},{"key":"e_1_2_12_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-4838(99)00152-1"},{"key":"e_1_2_12_56_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0030-1250120"},{"key":"e_1_2_12_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-46333-2"},{"key":"e_1_2_12_58_1","doi-asserted-by":"publisher","DOI":"10.1002\/iub.125"},{"key":"e_1_2_12_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2004.03.004"},{"key":"e_1_2_12_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2023.103038"},{"key":"e_1_2_12_61_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.485896"},{"key":"e_1_2_12_62_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-02287-x"},{"key":"e_1_2_12_63_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-29143-5"},{"key":"e_1_2_12_64_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-42202-0"},{"key":"e_1_2_12_65_1","doi-asserted-by":"publisher","DOI":"10.1093\/glycob\/10.12.1283"},{"key":"e_1_2_12_66_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1996.0832r.x"},{"key":"e_1_2_12_67_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-016-2247-5"},{"key":"e_1_2_12_68_1","doi-asserted-by":"publisher","DOI":"10.1080\/09168451.2014.943651"},{"key":"e_1_2_12_69_1","doi-asserted-by":"publisher","DOI":"10.21873\/invivo.13176"},{"key":"e_1_2_12_70_1","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.jbchem.a021909"},{"key":"e_1_2_12_71_1","doi-asserted-by":"publisher","DOI":"10.1271\/bbb.70612"},{"key":"e_1_2_12_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2020.03.176"},{"key":"e_1_2_12_73_1","doi-asserted-by":"publisher","DOI":"10.1128\/jb.175.22.7138-7141.1993"},{"key":"e_1_2_12_74_1","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.27.8.1859"},{"key":"e_1_2_12_75_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0007114517001866"},{"key":"e_1_2_12_76_1","doi-asserted-by":"publisher","DOI":"10.1038\/330379a0"},{"key":"e_1_2_12_77_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M108286200"},{"key":"e_1_2_12_78_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2015.05.005"},{"key":"e_1_2_12_79_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mam.2012.07.001"},{"key":"e_1_2_12_80_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-4165(00)00025-8"},{"key":"e_1_2_12_81_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00592-017-1093-8"},{"key":"e_1_2_12_82_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)36933-8"},{"key":"e_1_2_12_83_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.4c07718"},{"key":"e_1_2_12_84_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1718635115"},{"key":"e_1_2_12_85_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00191.2015"},{"key":"e_1_2_12_86_1","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.72.2.1248-1257.2006"},{"key":"e_1_2_12_87_1","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.jbchem.a122210"},{"key":"e_1_2_12_88_1","first-page":"E423","article-title":"Mechanism for Acute Reduction of 1,5\u2010Anhydroglucitol in Rats Treated With Diabetogenic Agents","volume":"258","author":"Yamanouchi T.","year":"1990","journal-title":"American Journal of Physiology"},{"key":"e_1_2_12_89_1","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.jbchem.a124922"},{"key":"e_1_2_12_90_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)65385-2"},{"key":"e_1_2_12_91_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-819460-7.00034-7"},{"key":"e_1_2_12_92_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00055.2009"},{"key":"e_1_2_12_93_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2011.12.027"},{"key":"e_1_2_12_94_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0056681"},{"key":"e_1_2_12_95_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3809"},{"key":"e_1_2_12_96_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2023.1145111"},{"key":"e_1_2_12_97_1","doi-asserted-by":"publisher","DOI":"10.2337\/diab.38.6.723"},{"key":"e_1_2_12_98_1","doi-asserted-by":"publisher","DOI":"10.1016\/0168-8227(94)90259-3"},{"key":"e_1_2_12_99_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00277486"},{"key":"e_1_2_12_100_1","doi-asserted-by":"publisher","DOI":"10.1002\/ctm2.470"},{"key":"e_1_2_12_101_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gim.2022.04.001"},{"key":"e_1_2_12_102_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-020-01503-8"},{"key":"e_1_2_12_103_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmd2.12364"},{"key":"e_1_2_12_104_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1463-1326.2011.01517.x"},{"key":"e_1_2_12_105_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13340-020-00472-4"},{"key":"e_1_2_12_106_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-019-01150-9"},{"key":"e_1_2_12_107_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2006.11.056"},{"key":"e_1_2_12_108_1","doi-asserted-by":"publisher","DOI":"10.1186\/1824-7288-40-30"},{"key":"e_1_2_12_109_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humimm.2025.111268"},{"key":"e_1_2_12_110_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.01485"},{"key":"e_1_2_12_111_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1601946"}],"container-title":["Journal of Inherited Metabolic Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jimd.70085","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jimd.70085","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jimd.70085","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:05:07Z","timestamp":1784678707000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jimd.70085"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9]]},"references-count":110,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2025,9]]}},"alternative-id":["10.1002\/jimd.70085"],"URL":"https:\/\/doi.org\/10.1002\/jimd.70085","archive":["Portico"],"relation":{},"ISSN":["0141-8955","1573-2665"],"issn-type":[{"value":"0141-8955","type":"print"},{"value":"1573-2665","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9]]},"assertion":[{"value":"2025-05-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-16","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70085"}}