Veiga-da-Cunha Maria, Gannoun Lila, Dewulf Joseph, Van Schaftingen Emile
Metabolic Research Group, de Duve Institute and UCLouvain, Brussels, Belgium.
Biochemical Genetics and Newborn Screening Laboratory, Department of Laboratory Medicine, Cliniques Universitaires Saint-Luc, UCLouvain, Brussels, Belgium.
J Inherit Metab Dis. 2025 Sep;48(5):e70085. doi: 10.1002/jimd.70085.
Neutropenia in Glycogen Storage Disease Type Ib (GSDIb) and G6PC3 deficiency results from defects in metabolite repair, leading to the accumulation of 1,5-anhydroglucitol-6-phosphate (1,5-AG6P). Treatment currently relies on inhibitors of SGLT2, the renal sodium-glucose co-transporter, which indirectly enhances urinary excretion of 1,5-anhydroglucitol (1,5-AG), the precursor of the toxic 1,5-AG6P 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-AG is essential. Here, we review the current knowledge of these mechanisms, their role in the pathophysiology of 1,5-AG6P-related neutropenia, and explore potential strategies to improve treatment outcomes.
1b型糖原贮积病（GSDIb）和葡萄糖-6-磷酸酶催化亚基3（G6PC3）缺乏症中的中性粒细胞减少是由代谢物修复缺陷导致的，会引起1,5-脱水葡萄糖醇-6-磷酸（1,5-AG6P）的积累。目前的治疗依赖于钠-葡萄糖协同转运蛋白2（SGLT2）抑制剂，该蛋白是一种肾脏钠-葡萄糖共转运体，它间接增强了1,5-脱水葡萄糖醇（1,5-AG）的尿排泄，1,5-AG是有毒的1,5-AG6P的前体，1,5-AG6P在中性粒细胞中积累，是这些患者中性粒细胞减少的根源。在此背景下，详细了解1,5-AG的形成、肠道吸收、肾脏重吸收和代谢至关重要。在这里，我们综述了这些机制的现有知识、它们在1,5-AG6P相关中性粒细胞减少症病理生理学中的作用，并探索改善治疗效果的潜在策略。
