Presymptomatic late-onset Pompe disease: Optimizing the timing of treatment

Abstract

Late-onset Pompe disease (LOPD) is a genetic myopathy causing severe limb girdle and diaphragmatic weakness. Pre-symptomatic diagnosis of LOPD is increasing. Enzyme replacement therapy (ERT) has shown dramatic efficacy in infantile-onset forms of the disease, supporting early diagnosis and treatment initiation, whereas the benefit of ERT on muscle weakness and respiratory insufficiency is moderate and not sustained over time in LOPD, raising questions about presymptomatic screening. Here, we present three presymptomatic cases of LOPD, showing that clinical symptoms can occur long after the diagnosis, resulting in a close monitoring without the need for treatment over several years. Several tests, such as walking tests, pulmonary function tests or whole-body muscle magnetic resonance imaging are sensitive for detecting early disease progression. Current guidelines provide no clear recommendations regarding the optimal timing of treatment initiation in presymptomatic patients. Nevertheless, in the context of a disease with a highly variable course, regular clinical, physiological and radiological assessments of each patient may allow for early detection of disease progression and support the decision to initiate treatment.

Keywords: Enzyme replacement therapy; Late-onset Pompe disease; Muscle MRI; Presymptomatic diagnosis.