A young woman with dramatic pulmonary hypertension and respiratory failure: a case report

Acid α-glucosidase (GAA) is the sole lysosomal enzyme responsible for degrading glycogen into glucose monomers. Deficiency of GAA leads to progressive lysosomal glycogen accumulation and cellular dysfunction, resulting in Pompe disease (PD), an autosomal recessive disorder. This case report described a 41-year-old woman who presented with progressive dyspnea and decreased exercise tolerance. The preliminary examination in the outpatient clinic showed that the patient suffered from pulmonary hypertension (PH). After the patient was admitted to the hospital and further relevant auxiliary examinations were completed, and finally a diagnosis of late-onset Pompe disease (LOPD) was confirmed. Protein structure prediction suggested that the double mutation might disrupt the hydrogen bond network, hydrophobic core, and aromatic interactions of the GAA enzyme, potentially reducing the stability of the protein (ΔΔG = -2.55 kcal/mol). Although these computational insights provide a theoretical basis for the clinical phenotype, they require further validation. This is a rare case of PD complicated with PH in the absence of childhood symptoms, suggesting that specific missense mutations may contribute to late-onset and milder phenotypes. This case underscores that clinicians should strengthen clinical discrimination when diagnosing respiratory failure and PH. Understanding the characteristics of infantile-onset Pompe disease (IOPD)-relatively mild enzymatic activity impairment and late onset-helps in the clinical management of genetic metabolic.