Treatment recommendations for glycogen storage disease type IB- associated neutropenia and neutrophil dysfunction with empagliflozin: Consensus from an international workshop.

Sarah C Grünert, Dorota Wesol-Kucharska, Blair Schneider, Enrique Landelino Contreras, Jamas LaFreniere, Sema Kalkan Uçar, Karolina M Stepien, Terry G J Derks, Alessandro Rossi, Peter Hofbauer, Ronen Spiegel, R Neil Dalton, Saskia B Wortmann, Surekha Pendyal, Helen Mundy, Neil Jones, Jean Donadieu, Maria Veiga-da-Cunha

Journal: Molecular genetics and metabolism 2024;141(3):108144

PMID: 38277989

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Abstract

Glycogen storage disease type Ib (GSD Ib, biallelic variants in SLC37A4) is a rare disorder of glycogen metabolism complicated by neutropenia/neutrophil dysfunction. Since 2019, the SGLT2-inhibitor empagliflozin has provided a mechanism-based treatment option for the symptoms caused by neutropenia/neutrophil dysfunction (e.g. mucosal lesions, inflammatory bowel disease). Because of the rarity of GSD Ib, the published evidence on safety and efficacy of empagliflozin is still limited and does not allow to develop evidence-based guidelines. Here, an international group of experts provides 14 best practice consensus treatment recommendations based on expert practice and review of the published evidence. We recommend to start empagliflozin in all GSD Ib individuals with clinical or laboratory signs related to neutropenia/neutrophil dysfunction with a dose of 0.3-0.4 mg/kg/d given as a single dose in the morning. Treatment can be started in an outpatient setting. The dose should be adapted to the weight and in case of inadequate clinical treatment response or side effects. We strongly recommend to pause empagliflozin immediately in case of threatening dehydration and before planned longer surgeries. Discontinuation of G-CSF therapy should be attempted in all individuals. If available, 1,5-AG should be monitored. Individuals who have previously not tolerated starches should be encouraged to make a new attempt to introduce starch in their diet after initiation of empagliflozin treatment. We advise to monitor certain safety and efficacy parameters and recommend continuous, alternatively frequent glucose measurements during the introduction of empagliflozin. We provide specific recommendations for special circumstances like pregnancy and liver transplantation.

Address: Department of General Pediatrics, Adolescent Medicine and Neonatology, Medical Centre- University of Freiburg, Faculty of Medicine, Freiburg, Germany.; Section of Metabolic Diseases, Beatrix Children's Hospital, University Medical Center of Groningen, University of Groningen, Hanzeplein 1, 9700 RB Groningen, the Netherlands.; Evelina London Children's Hospital, London, UK.; Centre de reference des neutropénies chroniques, Paris Sorbonne Université, Assistance Publique des Hopitaux de Paris, Hopital Trousseau, Paris 75012, France.; Department of Production, Landesapotheke Salzburg, Hospital Pharmacy, Salzburg, Austria.; University Children's Hospital Salzburg, Paracelsus Medical University and Salzburger Landeskliniken, Salzburg, Austria.; Division of Metabolism and Nutrition, Department of Pediatrics, Ege University Children's Hospital, Izmir, Turkey.; Sophie's Hope Foundation, Hopkinton, MA, USA; curegsd1b.org.; www.ninalaguerrera.org.; Duke University Medical Center, Durham, NC, USA.; Department of Translational Medicine, Section of Paediatrics, University of Naples "Federico II", Naples, Italy.; Sophie's Hope Foundation, Hopkinton, MA, USA.; Pediatric Department B, Emek Medical Center, Afula, Rappaport School of Medicine, Technion, Haifa, Israel.; Adult Inherited Metabolic Diseases, Salford Royal Organisation, Northern Care Alliance NHS Foundation Trust, M6 8HD Salford, Greater Manchester, United Kingdom.; Department of Pediatrics, Nutrition, and Metabolic Diseases, Children's Memorial Health Institute, Warsaw, Poland.; Groupe de Recherches Metaboliques, de Duve Institute, UCLouvain (Université Catholique de Louvain), B-1200 Brussels, Belgium.; University Children's Hospital Salzburg, Paracelsus Medical University and Salzburger Landeskliniken, Salzburg, Austria; Amalia Children's Hospital, Nijmegen, the Netherlands. Electronic address: [email protected].

DOI: 10.1016/j.ymgme.2024.108144

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MeSH Terms: Humans, Neutrophils, Consensus, Glycogen Storage Disease Type I, Neutropenia, Monosaccharide Transport Proteins, Antiporters, Benzhydryl Compounds, Glucosides