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. 2025 Jun 19.
doi: 10.1007/s40291-025-00795-5. Online ahead of print.

Clinical and Genetic Profile of 35 Patients with Glycogen Storage Disease Type 1b: A Comparative Analysis Before and During SGLT2 Inhibitor Therapy

Maja Djordjevic Milosevic  1   2 , Anita Skakic  3 , Bozica Kecman  4 , Sara Stankovic  3 , Ivona Kovacevic  5 , Sonja Pavlovic  3 , Maja Stojiljkovic  3
Affiliations

Clinical and Genetic Profile of 35 Patients with Glycogen Storage Disease Type 1b: A Comparative Analysis Before and During SGLT2 Inhibitor Therapy

Maja Djordjevic Milosevic et al. Mol Diagn Ther. .

Abstract

Background: Glycogen storage disease type 1b (GSD 1b) is an ultra-rare disease worldwide, whereas in Serbia it has an unexpectedly high prevalence. GSD 1b is the result of variants in the SLC37A4 gene and reduced function of the enzyme glucose 6 phosphate translocase (G6PT). In addition to the classic symptoms of GSD 1a, patients with GSD 1b have neutropenia and impaired neutrophil function.

Methods: The genotype and clinical profile were analyzed in 35 patients, 26 of whom were children. In all patients, pathogenic variants in the SLC37A4 gene were confirmed using Sanger or next-generation sequencing (NGS). Eight different variants were found. The following clinical data were analyzed: age at diagnosis, first symptoms of GSD 1b, severity of intestinal symptoms, lowest neutrophil count, mean hemoglobin value, height, body mass index (BMI), and quality of life. Patients were classified into four groups based on the severity of their intestinal symptoms.

Results: In our study 30 patients received empagliflozin therapy. Our data are comprised of information from a total of 62 treatment years and include self-reported quality-of-life surveys before and during empagliflozin therapy. The average age at which empagliflozin was introduced in pediatric patients was 8.5 years, with the youngest two patients, both female, starting SGLT2 inhibitor therapy at the age of two.

Conclusions: Our findings suggest that empagliflozin therapy significantly improves neutropenia recovery by reducing the frequency of recurrent infections and inflammatory bowel disease (IBD)-like symptoms. This improvement was demonstrated by a marked reduction in skin and mucosal infections, particularly oral ulcers, as well as an increase in hemoglobin levels and overall stature.

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Conflict of interest statement

Declarations. Funding: This work was supported by the Science Fund of the Republic of Serbia, Prisma program, Grant Number 6999 and Ministry of Science, Technological Development and Innovation of the Republic of Serbia [Number: 451-03-136/2025-03/200042]. Conflict of Interest: The authors MDjM, AS, BK, SS, IK, SP, MS declare no competing interests. Ethics Approval: This study has been approved by the Ethics Approval Committee of the Mother and Child Health Care Institute of Serbia “Dr Vukan Cupic” in Belgrade, Serbia (8/2025 and 31/2020). Human Ethics and Consent to Participate: The study was performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. Informed consent was obtained from all individual participants included in the study. Data Availability: Raw genetic data are generated and stored at Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, and are available on reasonable request. Authors’ Contributions: MDj conceived the study, collected all data, performed analysis, wrote the paper; AS performed the genetic analysis and wrote the paper; SS prepared all figures; BK and IK collected the patients’ phenotype data; SP reviewed the paper; MS wrote the paper.

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References

    1. Kishnani PS, Austin SL, Abdenur JE, et al. Diagnosis and management of glycogen storage disease type I: a practice guideline of the American College of Medical Genetics and Genomics. Genet Med. 2014;16(11): e1. https://doi.org/10.1038/gim.2014.128 . - DOI - PubMed
    1. Rake JP, Visser G, Labrune P, et al. Glycogen storage disease type I: diagnosis, management, clinical course and outcome. Results of the European Study on Glycogen Storage Disease Type I (ESGSD I). Eur J Pediatr. 2002;161(Suppl 1):20–34. https://doi.org/10.1007/s00431-002-0999-4 . - DOI
    1. Chou JY, Jun HS, Mansfield BC. Type I glycogen storage diseases: disorders of the glucose-6-phosphatase/glucose-6-phosphate transporter complexes. J Inherit Metab Dis. 2015;38(3):511–9. https://doi.org/10.1007/s10545-014-9772-x . - DOI - PubMed
    1. Froissart R, Piraud M, Boudjemline AM, et al. Glucose-6-phosphatase deficiency. Orphanet J Rare Dis. 2011;6:27. https://doi.org/10.1186/1750-1172-6-27- . - DOI - PubMed - PMC
    1. Chena MA, Weinstein DA. Glycogen storage diseases: diagnosis, treatment and outcome. Transl Sci Rare Dis. 2016;1:45–72. https://doi.org/10.3233/TRD-160006 . - DOI

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