Interplay between mitochondrial dysfunction and lysosomal storage: challenges in genetic metabolic muscle diseases with a focus on infantile onset Pompe disease

Background Pompe disease (PD) is a rare, progressive autosomal recessive lysosomal storage disorder that directly impacts mitochondrial function, leading to structural abnormalities and potentially culminating in heart failure or cardiogenic shock. The clinical course and molecular mechanisms of the disease remain incompletely understood. Methods We performed a retrospective analysis to examine the clinical manifestations, genetic traits, and the relationship between PD and mitochondrial function in a pediatric patient. This comprehensive evaluation included the use of ultrasound echocardiograms, computed tomography (CT) scans, electrocardiograms, mutagenesis analysis, and structural analysis to gain insights into the patient's condition and the underlying mechanisms of PD. For structural analysis and visualization, the structure of protein data bank ID 5KZX of human GAA was used, and VMD software was used for visualization and analysis. Results The study revealed that a 5-month-old male infant was admitted due to fever, with physical examination finding abnormal cardiopulmonary function and hepatomegaly. Laboratory tests and echocardiography confirmed heart failure and hypertrophic cardiomyopathy. Despite a week of treatment, which normalized body temperature and reduced pulmonary inflammation, cardiac abnormalities did not show significant improvement. Further genetic testing identified a homozygous mutation c.2662GT (p.E888) in the GAA gene, leading to a diagnosis of Infantile-Onset Pompe Disease (IOPD). Conclusions Although enzyme replacement therapy can significantly improve the quality of life for patients with PD, enhancing mitochondrial function may represent a new therapeutic strategy for treating PD.