Cardiac Pathology in Glycogen Storage Disease Type III

Abstract

Purpose: To investigate the distribution and clinical impact of glycogen accumulation on heart structure and function in individuals with GSD III.Methods: We examined cardiac tissue and the clinical records of three individuals with GSD IIIa who died or underwent cardiac transplantation. Of the two patients that died, one was from infection and the other was from sudden cardiac death. The third patient required cardiac transplantation for end-stage heart failure with severe hypertrophic cardiomyopathy.

Rescue of GSDIII Phenotype with Gene Transfer Requires Liver- and Muscle-Targeted GDE Expression

“…CMV promoter-driven GDE transgene expression mediated the complete rescue of muscle function and glycogen accumulation in different muscle groups, including the heart. 36 Biochemical parameters correlated with muscle histology and PAS staining, which showed good correction of the disease phenotype. Conversely, due to the silencing of the CMV promoter in liver, 23 no liver GDE expression was detected and no corrections of glycogen accumulation, hepatomegaly, or glycemia were observed, indicating that targeting muscle alone would not rescue the metabolic impairment hallmark of GSDIII.…”

Skeletal and cardiac muscle involvement in children with glycogen storage disease type III

“…There is no reliable method to predict which patient will have cardiac involvement or progress to cardiomyopathy. Cardiac magnetic resonance imaging could detect the extent of cardiac fibrosis and indicate those patients at higher risk for life threatening arrhythmias [2]. Life-threatening cardiac arrhythmias have been reported in rare instances in patients with GSD III [7].…”

Postmortem Findings and Clinical Correlates in Individuals with Infantile-Onset Pompe Disease

“…Several longterm survivors have experienced arrhythmias (McDowell et al 2008;Prater et al 2012), and we propose that cardiac conduction is affected by glycogen accumulation within the conduction system. Glycogen accumulation in the cardiac conduction system is present in glycogen storage disease type III and in the mouse model for PRKAG2-caused hypertrophic cardiomyopathy (Austin et al 2012;Arad et al 2003). Persistence of glycogen in cardiac conduction tissue, despite ERT, suggests poor penetration and a potential cardiac cause for sudden death in cases 1 and 3.…”