Neutropenia, neutrophil dysfunction, and inflammatory bowel disease in glycogen storage disease type Ib: Results of the European Study on Glycogen Storage Disease Type I

2000 ◽  
Vol 137 (2) ◽  
pp. 187-191 ◽  
Author(s):  
Gepke Visser ◽  
Jan-Peter Rake ◽  
John Fernandes ◽  
Philippe Labrune ◽  
James V. Leonard ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Glycogen Storage Disease ◽  
Storage Disease ◽  
Glycogen Storage Disease Type ◽  
Glycogen Storage ◽  
Disease Type ◽  
Type I ◽  
European Study ◽  
Inflammatory Bowel ◽  
Neutrophil Dysfunction

Inflammatory Bowel Disease in Glycogen Storage Disease Type Ia

2017 ◽  
Vol 64 (2) ◽  
pp. e52-e54 ◽  
Author(s):  
Nicole T. Lawrence ◽  
Tayoot Chengsupanimit ◽  
Laurie M. Brown ◽  
Terry G.J. Derks ◽  
G. Peter A. Smit ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Glycogen Storage Disease ◽  
Bowel Disease ◽  
Storage Disease ◽  
Glycogen Storage Disease Type ◽  
Glycogen Storage ◽  
Disease Type ◽  
Type Ia ◽  
Inflammatory Bowel

scholarly journals Treating neutropenia and neutrophil dysfunction in glycogen storage disease type Ib with an SGLT2 inhibitor

Blood ◽  
2020 ◽  
Vol 136 (9) ◽  
pp. 1033-1043 ◽  
Author(s):  
Saskia B. Wortmann ◽  
Johan L. K. Van Hove ◽  
Terry G. J. Derks ◽  
Nathalie Chevalier ◽  
Vijaya Knight ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Storage Disease ◽  
Sglt2 Inhibitor ◽  
Glycogen Storage Disease Type ◽  
Neutrophil Function ◽  
Glycogen Storage ◽  
Disease Type ◽  
Inflammatory Bowel ◽  
Neutrophil Dysfunction

Abstract Neutropenia and neutrophil dysfunction cause serious infections and inflammatory bowel disease in glycogen storage disease type Ib (GSD-Ib). Our discovery that accumulating 1,5-anhydroglucitol-6-phosphate (1,5AG6P) caused neutropenia in a glucose-6-phosphatase 3 (G6PC3)–deficient mouse model and in 2 rare diseases (GSD-Ib and G6PC3 deficiency) led us to repurpose the widely used antidiabetic drug empagliflozin, an inhibitor of the renal glucose cotransporter sodium glucose cotransporter 2 (SGLT2). Off-label use of empagliflozin in 4 GSD-Ib patients with incomplete response to granulocyte colony-stimulating factor (GCSF) treatment decreased serum 1,5AG and neutrophil 1,5AG6P levels within 1 month. Clinically, symptoms of frequent infections, mucosal lesions, and inflammatory bowel disease resolved, and no symptomatic hypoglycemia was observed. GCSF could be discontinued in 2 patients and tapered by 57% and 81%, respectively, in the other 2. The fluctuating neutrophil numbers in all patients were increased and stabilized. We further demonstrated improved neutrophil function: normal oxidative burst (in 3 of 3 patients tested), corrected protein glycosylation (2 of 2), and normal neutrophil chemotaxis (1 of 1), and bactericidal activity (1 of 1) under treatment. In summary, the glucose-lowering SGLT2 inhibitor empagliflozin, used for type 2 diabetes, was successfully repurposed for treating neutropenia and neutrophil dysfunction in the rare inherited metabolic disorder GSD-Ib without causing symptomatic hypoglycemia. We ascribe this to an improvement in neutrophil function resulting from the reduction of the intracellular concentration of 1,5AG6P.

Glycogen storage disease type I: diagnosis, management, clinical course and outcome. Results of the European study on glycogen storage disease type I (ESGSD I)

2002 ◽  
Vol 161 (1) ◽  
pp. S20-S34 ◽  
Author(s):  
Jan Peter Rake ◽  
Gepke Visser ◽  
Philippe Labrune ◽  
James V. Leonard ◽  
Kurt Ullrich ◽  
...  
Keyword(s):  
Glycogen Storage Disease ◽  
Storage Disease ◽  
Clinical Course ◽  
Glycogen Storage Disease Type ◽  
Glycogen Storage ◽  
Disease Type ◽  
Type I ◽  
European Study

Guidelines for management of glycogen storage disease type I—European study on glycogen storage disease type I (ESGSD I)

2002 ◽  
Vol 161 (1) ◽  
pp. S112-S119 ◽  
Author(s):  
Jan Peter Rake ◽  
Gepke Visser ◽  
Philippe Labrune ◽  
James V. Leonard ◽  
Kurt Ullrich ◽  
...  
Keyword(s):  
Glycogen Storage Disease ◽  
Storage Disease ◽  
Glycogen Storage Disease Type ◽  
Glycogen Storage ◽  
Disease Type ◽  
Type I ◽  
European Study

Guidelines for management of glycogen storage disease type I - European Study on Glycogen Storage Disease Type I (ESGSD I)

2002 ◽  
Vol 161 (0) ◽  
pp. S112-S119 ◽  
Author(s):  
Philippe Labrune ◽  
Kurt Ullrich ◽  
Peter Smit ◽  
Jan Rake ◽  
Gepke Visser ◽  
...  
Keyword(s):  
Glycogen Storage Disease ◽  
Storage Disease ◽  
Glycogen Storage Disease Type ◽  
Glycogen Storage ◽  
Disease Type ◽  
Type I ◽  
European Study

Inflammatory bowel disease in glycogen storage disease type Ib

1986 ◽  
Vol 109 (1) ◽  
pp. 55-59 ◽  
Author(s):  
Thomas F. Roe ◽  
Daniel W. Thomas ◽  
Vicente Gilsanz ◽  
Hart Isaacs ◽  
James B. Atkinson
Keyword(s):  
Inflammatory Bowel Disease ◽  
Glycogen Storage Disease ◽  
Bowel Disease ◽  
Storage Disease ◽  
Glycogen Storage Disease Type ◽  
Glycogen Storage ◽  
Disease Type ◽  
Inflammatory Bowel
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