Abstract
BACKGROUND: Late-onset Pompe disease (LOPD) is a rare autosomal recessive disorder caused by a deficiency of acid alpha-glucosidase (GAA), leading to progressive skeletal and respiratory muscle weakness. In about 10% of cases, diaphragmatic weakness may be the sole presenting feature. Early diagnosis is crucial, as ventilatory support improves outcomes and enzyme replacement therapy can slow disease progression. CASE PRESENTATION: A 60-year-old male with a medical history of heart failure presented with dyspnoea, orthopnoea and fluctuating visual hallucinations. Initial metabolic alkalosis, presumed secondary to diuretics, masked chronic hypercapnic respiratory failure. Despite optimised heart failure treatment, symptoms persisted. Pulmonary function tests showed a restrictive pattern with preserved diffusion. Hypercapnic respiratory failure prompted admission to the intensive care unit and invasive ventilation. A significant drop in vital capacity between upright and semi-recumbent positions and absent phrenic nerve responses indicated diaphragmatic weakness. Low GAA activity and genetic testing confirmed the diagnosis of LOPD. Neurological and immunological work-up excluded alternative causes. Non-invasive ventilation improved symptoms, and enzyme replacement therapy with avalglucosidase alfa was initiated. CONCLUSION: This case illustrates the diagnostic challenge of isolated respiratory failure due to LOPD when early signs are masked by comorbidities and metabolic disturbances. Nocturnal hypoventilation may cause atypical symptoms such as hallucinations. Systematic neuromuscular evaluation is essential to enable timely ventilatory support and disease-specific treatment. LEARNING POINTS: Isolated respiratory failure due to diaphragm weakness can be the first manifestation of late-onset Pompe disease.Diagnosing diaphragmatic weakness is challenging in cardiopulmonary disease, as symptoms may be misattributed.Visual hallucinations are a rare symptom of nocturnal hypoventilation.