Pompe Disease (GSD Type II): Biochemical Pathways (Critical Care Guideline)

■ LECTURE OVERVIEW: Pompe Disease (Glycogen Storage Disease Type II) is a lysosomal storage disease that impairs the degradation of a small fraction of cellular glycogen, leading to multi-organ tissue destruction. ■ METABOLIC INFRASTRUCTURE: 1. Enzymatic Void: Autosomal recessive deficiency of Lysosomal Acid Alpha-1,4-Glucosidase (also called acid maltase). 2. Compartment Sequestration: Unlike other glycogen storage diseases, the defect is localized within lysosomes, which take up intracellular glycogen via autophagy but are unable to hydrolyze its alpha-1,4 and alpha-1,6 linkages. 3. Intralysosomal Glycogen Aggregation: Glycogen accumulates selectively within lysosomal vacuoles of major metabolically active tissues, primarily cardiac, skeletal, and smooth muscle fibers. 4. Myofibril Displacement: Cellular organelles are displaced, and myofibrillar architecture is completely disrupted by hypertrophying lysosomes, causing early muscle destruction. ■ BIOCHEMICAL MECHANISMS: At the molecular level, enzyme kinetics govern reaction rates. Competitive inhibitors raise apparent Michaelis constants without changing maximum speed, whereas noncompetitive inhibitors decrease maximum speed directly. ■ CRITICAL CARE MANAGEMENT PROTOCOL: Continuous cardiopulmonary and metabolic monitoring is paramount during acute decompensation. Maintain strict control over fluid ratios and oxygenation parameters. [HY-BOARD-1090]