Unexplained Progressive Respiratory Insufficiency and Weakness Diagnosed as Late-Onset Pompe Disease Through Biochemical and Molecular Genetic Testing.

Late-onset Pompe disease is a rare autosomal recessive lysosomal storage disorder caused by acid α-glucosidase deficiency, resulting in progressive skeletal muscle weakness and respiratory failure. We present the case of a 43-year-old African American woman who was admitted to the intensive care unit with acute-on-chronic hypoxemic and hypercarbic respiratory failure, alteration of consciousness, and progressive weakness. Her recent medical history included respiratory distress and aspiration pneumonia, which had not fully resolved despite supplemental oxygen therapy. On admission, initial evaluations including imaging and laboratory tests did not reveal a diagnosis. Muscle biopsy showed a vacuolar myopathy with excess glycogen suggestive of glycogen storage disease. Enzyme testing was obtained through the dried blood spot testing and was low. Molecular genetic testing identified two pathogenic variants in the GAA gene, confirming the diagnosis of late-onset Pompe disease. This diagnosis enabled the prompt initiation of enzyme replacement therapy (ERT) with alglucosidase alpha. The early initiation of ERT in this patient was pivotal in managing her condition, given the progressive nature of late-onset Pompe disease and the potential for improved outcome when treatment is started early. This case highlights the importance of considering late-onset Pompe disease in adults presenting with unexplained progressive respiratory and neuromuscular symptoms. It also demonstrates the critical role of biochemical and molecular genetic testing, as early intervention can significantly impact treatment outcomes and quality of life.