Improved inflammatory bowel disease, wound healing and normal oxidative burst under treatment with empagliflozin in glycogen storage disease type Ib

Abstract

Background: Glycogen storage disease type Ib (GSD Ib) is a rare inborn error of glycogen metabolism due to mutations in SLC37A4. Besides a severe form of fasting intolerance, the disorder is usually associated with neutropenia and neutrophil dysfunction causing serious infections, inflammatory bowel disease, oral, urogenital and perianal lesions as well as impaired wound healing. Recently, SGLT2 inhibitors such as empagliflozin that reduce the plasma levels of 1,5-anhydroglucitol have been described as a new treatment option for the neutropenia and neutrophil dysfunction in patients with GSD Ib. Results: We report on a 35-year-old female patient with GSD Ib who had been treated with G-CSF for neutropenia since the age of 9. She had a large chronic abdominal wound as a consequence of recurrent operations due to complications of her inflammatory bowel disease. Treatment with 20 mg empagliflozin per day resulted in normalisation of the neutrophil count and neutrophil function even after termination of G-CSF. The chronic abdominal wound that had been unchanged for 2 years before the start of empagliflozin nearly closed within 12 weeks. No side effects of empagliflozin were observed. Conclusion: SGLT2 inhibitors are a new and probably safe treatment option for GSD Ib-associated neutropenia and neutrophil dysfunction. We hypothesize that restoration of neutrophil function and normalisation of neutrophil apoptosis leads to improvement of wound healing and ameliorates symptoms of inflammatory bowel disease.

The SGLT2-inhibitor dapagliflozin improves neutropenia and neutrophil dysfunction in a mouse model of the inherited metabolic disorder GSDIb

“…These results have consequently led to preliminary off-label use of empagliflozin in few GSDIb patients. Despite the rather low number of treated patients, the results obtained are very encouraging, demonstrating an approximate 6-fold decrease in the concentration of 1,5AG in plasma and of 1,5AG6P in neutrophils which leads to a good recovery of neutrophil activity and an improvement of GSDIb-associated symptoms [4] , [8] , [13] , [14] , [15] . Here, we report the results obtained in the GSDIb mouse model we have generated in terms of neutropenia and neutrophils' functional activity recovery upon treatment with the SGLT2 inhibitor dapagliflozin, an empagliflozin analog.…”

Crohn disease-like enterocolitis remission after empagliflozin treatment in a child with glycogen storage disease type Ib: a case report

“…Although previous reports have shown possible benefit of empagliflozin on gastrointestinal symptoms [ 12 , 13 ], follow-up data on bowel (macro/microscopic) morphology are not available. In the case herein reported, we presented comprehensive gastrointestinal assessment in a child with GSD Ib, showing clear benefit of empagliflozin administration on Chron disease-like enterocolitis.…”

“…Two recent reports have shown same effect in GSD Ib patients with improved neutrophil count/function. Possible benefit on gastrointestinal symptoms have also been reported [ 12 , 13 ]. However, no follow-up data on bowel (macro/microscopic) morphology are available.…”

Peritoneal inclusion cyst in a patient with glycogen storage disease type Ib and Crohn’s like disease

“…The patient is a 36-year-old woman who was diagnosed with GSD Ib at the age of 10 months. Details on the clinical course of the patient have been published previously (Grünert et al 2020). Dietary treatment with a calculated carbohydrate intake and nocturnal continuous feeds was started in infancy, and the patient has always remained in good metabolic control.…”