Phenotypic Expansion of GYG1 ‐Related Disease Presenting as Hypertrophic Cardiomyopathy With Brugada Phenocopy

Glycogen storage disease Type XV (GSD-XV; OMIM #613507) is an ultra-rare autosomal recessive disorder caused by biallelic pathogenic variants in GYG1, typically presenting with late-onset skeletal myopathy, while predominant cardiac involvement is exceptional. We report a 31-year-old man with chest pain, fatigue, and exertional dyspnea whose electrocardiogram demonstrated a spontaneous Type-1 Brugada pattern with complete right bundle branch block. Transthoracic echocardiography revealed nonobstructive left ventricular hypertrophy with preserved ejection fraction, whereas speckle-tracking showed markedly reduced global longitudinal strain with a heterogeneous distribution and absence of apical sparing. Cardiac magnetic resonance demonstrated mid-to-apical hypertrophy and patchy nonischemic late gadolinium enhancement consistent with myocardial fibrosis. Clinical exome sequencing identified a homozygous pathogenic GYG1 variant (NM_004130.4:c.304G>C; p.(Asp102His)) supported by functional evidence and familial segregation consistent with autosomal recessive inheritance. No pathogenic variants were detected in genes classically associated with Brugada syndrome, supporting a substrate-related Brugada phenocopy. Neurological examination, serum creatine kinase levels, and systemic evaluation were unremarkable. This case further expands the recognized cardiac phenotype associated with GYG1 deficiency by illustrating the coexistence of metabolic hypertrophic cardiomyopathy, myocardial fibrosis, and a Brugada phenocopy pattern, while highlighting a potential link between structural remodeling and arrhythmogenic electrical manifestations.