Unraveling the Genetic Basis of Glycogen Storage Diseases through Exome Sequencing: A Study in Pediatric Patients

Introduction: Glycogen Storage Diseases (GSDs) are a group of inherited metabolic disorders characterized by impaired glycogen metabolism, primarily affecting the liver and muscles. Methods: A retrospective cross-sectional study was conducted. Medical records of 72 children afflicted with GSDs were reviewed for clinical features, family history, and consanguinity. Sequencing was performed using DNA samples from patients and their family members. Results: Of the 72 patients, median age at presentation was 5.0 months (IQR: 1.8–9.0). Common features included abdominal distension (97.2%), hepatomegaly (94.4%), doll-like facies (54.2%), and failure to thrive (53%). Other findings included acidotic breathing, developmental delay, vomiting, convulsions, and positive family history. All cases involved consanguinity. Thirty-eight pathogenic variants were identified across nine GSD-associated genes. Conclusion: Abdominal distension, hepatomegaly, and failure to thrive are key clinical indicators of GSDs. Genetic testing improves diagnostic accuracy and classification, and our findings expand the mutational spectrum of GSDs in Pakistan.