Acid alpha-glucosidase (GAA) (GAA)

Acid alpha-glucosidase (GAA) is a critical lysosomal enzyme responsible for the breakdown of glycogen into glucose within the acidic environment of the lysosome (UniProt P10253). This enzyme is the sole catalyst for lysosomal glycogen degradation, a process distinct from cytosolic glycogenolysis. A deficiency or total absence of GAA leads to Pompe disease, a progressive multisystemic disorder characterized by the toxic accumulation of glycogen in various tissues, most notably cardiac and skeletal muscle (NIH GARD). This accumulation leads to progressive muscle weakness, respiratory insufficiency, and, in infantile-onset cases, hypertrophic cardiomyopathy. Therapeutic strategies primarily focus on enzyme replacement therapy (ERT), where recombinant human GAA is administered to clear lysosomal glycogen stores (FDA). Newer treatments also utilize pharmacological chaperones to enhance the stability and delivery of the enzyme to the target tissues (PubMed PMC10504657). Monitoring treatment efficacy often involves measuring urinary biomarkers like glucose tetrasaccharide and muscle enzyme levels to assess the reduction of glycogen burden (PubMed PMC4339234).

Other names

Acid maltaseLysosomal alpha-glucosidaseAglucosidase alfa1,4-alpha-glucosidase

Enzyme replacement therapy (ERT) involves the intravenous administration of recombinant human GAA to restore lysosomal glycogen degradation (FDA). Pharmacological chaperones like miglustat are used to stabilize the enzyme and enhance its delivery to lysosomes (PubMed PMC10504657).