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

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.