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

Sarah C Grünert,Stefanie Rosenbaum-Fabian,Roland Elling,Luciana Hannibal,Bärbel Maag,Ute Spiekerkoetter,Saskia B Wortmann,Anke Schumann,Terry G J Derks

doi:10.1186/s13023-020-01503-8

Abstract

BackgroundGlycogen 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.ResultsWe 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.ConclusionSGLT2 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.

Highlights

Glycogen storage disease type Ib (GSD Ib) is a rare inborn error of glycogen metabolism due to mutations in SLC37A4
Glycogen storage disease type Ib (GSD Ib) is a rare disorder of glycogen metabolism due to mutations in SLC37A4 encoding the glucose-6-phosphate transporter of the endoplasmic reticulum
Case report The patient is a 35 year-old woman who was diagnosed with GSD Ib at the age of 10 months

Summary

Introduction

Glycogen storage disease type Ib (GSD Ib) is a rare inborn error of glycogen metabolism due to mutations in SLC37A4. 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. Glycogen storage disease type Ib (GSD Ib) is a rare disorder of glycogen metabolism due to mutations in SLC37A4 encoding the glucose-6-phosphate transporter of the endoplasmic reticulum. Glycogen storage disease type Ib (GSD Ib) is a rare disorder of glycogen metabolism due to mutations in SLC37A4 encoding the glucose-6-phosphate transporter of the endoplasmic reticulum This glucose-6-phosphate transporter is ubiquitously expressed and transports glucose-6-phosphate from the cytosol to the lumen of the endoplasmic reticulum where it can be hydrolyzed by glucose-6-phosphatase [1]. Neutropenia is the hallmark feature of GSD Ib, the age at onset as well as the clinical course are variable [3]. It may be present already at birth or not appear until late in childhood as cyclic or permanent neutropenia [3, 4]

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