Glycogen Storage Disease Type II

Excerpt

Glycogen storage disease type II, also known as Pompe disease, is a rare and progressive neuromuscular disorder inherited in an autosomal recessive manner. This disease results from a deficiency of the enzyme acid α-glucosidase (GAA), causing impairment in the degradation of glycogen within the lysosomes of the muscular tissue.

The clinical presentation of glycogen storage disease type II varies widely depending on the age of symptom onset, the degree of GAA deficiency, and the specific mutations involved. Two phenotypes are described: infantile-onset Pompe disease (IOPD), which is the classic and more severe form, and late-onset Pompe disease (LOPD), which may manifest later in childhood or adulthood. IOPD typically presents within the first few months of life with severe symptoms, eg, hypotonia, hypertrophic cardiomyopathy, and respiratory failure; this last symptom remains the leading cause of mortality. LOPD presents more insidiously, often with proximal muscle weakness and eventual respiratory insufficiency due to diaphragm involvement, while cardiac and gastrointestinal symptoms are rare.

Pompe disease diagnosis is confirmed through genetic testing, identifying pathogenic mutations in the GAA gene, and enabling the cross-reactive immunologic material (CRIM) status determination. CRIM status is crucial for assessing residual GAA protein production and is strongly associated with prognosis and response to enzyme replacement therapy. Early detection and treatment, particularly in newborns, significantly alter the disease course, with enzyme replacement therapy (ERT) remaining the cornerstone of management.