ArticleJournal of inherited metabolic disease2022
Successful use of empagliflozin to treat neutropenia in two G6PC3-deficient children: Impact of a mutation in SGLT5.
Article in Journal of inherited metabolic disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.
- Dapagliflozin and Empagliflozin in Paediatric Indications: A Systematic Review.Paediatric drugs · 2024Pooled it
- Shifting Towards Empagliflozin First-Line Therapy in Glycogen Storage Disease Type Ib: A Nationwide Real-World Study.Journal of inherited metabolic disease · 2026Article
- Insights into Neutrophil Dysfunction in Inherited Metabolic Disorders.Journal of innate immunity · 2026Review
- Pathophysiology of the Neutropenia of GSDIb and G6PC3 Deficiency: Origin, Metabolism and Elimination of 1,5-Anhydroglucitol.Journal of inherited metabolic disease · 2025Review
- High-Fructose-Induced Salt-Sensitive Hypertension: The Potential Benefit of SGLT4 or SGLT5 Modulation.Nutrients · 2025Review
- SGLT2 Inhibitors: From Structure-Effect Relationship to Pharmacological Response.International journal of molecular sciences · 2025Review
- Empagliflozin as treatment in glycogen storage disease type IB patients.Molecular genetics and metabolism reports · 2025Article
- Article
- Biochemical characterization of the human ubiquitous glucose-6-phosphatase in neutrophil granulocytes.FEBS open bio · 2025Article
- Molecular and Clinical Characterization of a Founder Mutation Causing G6PC3 Deficiency.Journal of clinical immunology · 2024Article
- The Potential Impact of SGLT2-I in Diabetic Foot Prevention: Promising Pathophysiologic Implications, State of the Art, and Future Perspectives-A Narrative Review.Medicina (Kaunas, Lithuania) · 2024Review
- Molecular and clinical characterization of a founder mutation causing G6PC3 deficiency.Research square · 2024Article
- Refractory wound healing and cytopenias treated with a sodium-glucose cotransporter-2 inhibitor in a patient with glucose-6-phosphatase catalytic subunit 3 deficiency.JAAD case reports · 2024Article
- Molecular and clinical characterization of a founder mutation causing G6PC3 deficiency.medRxiv : the preprint server for health sciences · 2024Article
- Drug Safety Evaluation of Sodium-Glucose Cotransporter 2 Inhibitors in Diabetic Comorbid Patients by Review of Systemic Extraglycemic Effects.Diabetes, metabolic syndrome and obesity : targets and therapy · 2024Review
- SGLT5 is the renal transporter for 1,5-anhydroglucitol, a major player in two rare forms of neutropenia.Cellular and molecular life sciences : CMLS · 2023Article
- Glycogen storage diseases: An update.World journal of gastroenterology · 2023Review
- Severe congenital neutropenia due to G6PC3 deficiency: early and delayed phenotype of a patient.Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology · 2023Article
- Liver transplantation in glycogen storage disease type Ib: The role of SGLT2 inhibitors.Molecular genetics and metabolism reports · 2023Article
- Treatment of the Neutropenia Associated with GSD1b and G6PC3 Deficiency with SGLT2 Inhibitors.Diagnostics (Basel, Switzerland) · 2023Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neutropenia and neutrophil dysfunction found in deficiencies in G6PC3 and in the glucose-6-phosphate transporter (G6PT/SLC37A4) are due to accumulation of 1,5-anhydroglucitol-6-phosphate (1,5-AG6P), an inhibitor of hexokinase made from 1,5-anhydroglucitol (1,5-AG), an abundant polyol present in blood. Lowering blood 1,5-AG with an SGLT2 inhibitor greatly improved neutrophil counts and function in G6PC3-deficient mice and in patients with G6PT-deficiency. We evaluate this treatment in two G6PC3-deficient children. While neutropenia was severe in one child (PT1), which was dependent on granulocyte cololony-stimulating factor (GCSF), it was significantly milder in the other one (PT2), which had low blood 1,5-AG levels and only required GCSF during severe infections. Treatment with the SGLT2-inhibitor empagliflozin decreased 1,5-AG in blood and 1,5-AG6P in neutrophils and improved (PT1) or normalized (PT2) neutrophil counts, allowing to stop GCSF. On empagliflozin, both children remained infection-free (>1 year - PT2; >2 years - PT1) and no side effects were reported. Remarkably, sequencing of SGLT5, the gene encoding the putative renal transporter for 1,5-AG, disclosed a rare heterozygous missense mutation in PT2, replacing the extremely conserved Arg401 by a histidine. The higher urinary clearance of 1,5-AG 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-deficiency.
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