Successful use of empagliflozin to treat neutropenia in two G6PC3‐deficient children: Impact of a mutation in SGLT5

• DOI: 10.1002/jimd.12509
• Publication Date: 2022-05-04T09:41:10Z
• Authors: Cécile Boulanger; Xavier Stephenne; Jennifer Diederich; Pierre Mounkoro; Nathalie Chevalier; Alina Ferster; Emile Van Schafti...; Maria Veiga‐da‐Cunha
• Keywords: Empagliflozin

Abstract Neutropenia and neutrophil dysfunction found in deficiencies G6PC3 the glucose‐6‐phosphate transporter (G6PT/SLC37A4) are due to accumulation of 1,5‐anhydroglucitol‐6‐phosphate (1,5‐AG6P), an inhibitor hexokinase made from 1,5‐anhydroglucitol (1,5‐AG), abundant polyol present blood. Lowering blood 1,5‐AG with SGLT2 greatly improved counts function G6PC3‐deficient mice patients G6PT‐deficiency. We evaluate this treatment two children. While neutropenia was severe one child (PT1), which dependent on granulocyte cololony‐stimulating factor (GCSF), it significantly milder other (PT2), had low levels only required GCSF during infections. Treatment SGLT2‐inhibitor empagliflozin decreased 1,5‐AG6P neutrophils (PT1) or normalized (PT2) counts, allowing stop GCSF. On empagliflozin, both children remained infection‐free (>1 year – PT2; >2 years PT1) no side effects were reported. Remarkably, sequencing SGLT5, gene encoding putative renal for 1,5‐AG, disclosed a rare heterozygous missense mutation PT2, replacing extremely conserved Arg401 by histidine. The higher urinary clearance explains more benign outstanding response child. Our data shows that inhibitors excellent alternative treat G6PC3‐deficiency.