2025/09/01 by Maria Veiga‐da‐Cunha, Lila Gannoun, Joseph P. Dewulf +1 · 1 voice
Biochemistry, Genetics and Molecular Biology · Medicine · #Blood disorders and treatments #Glycogen Storage Diseases and Myoclonus #Neonatal Health and Biochemistry
paper · pdf · doi:10.1002/jimd.70085
openalex publication_date 2025/09/01 · openalex created_date 2025/09/18 · openalex updated_date 2026/07/15
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.