Management of musculoskeletal issues in Pompe disease

Pompe disease (PD) is an autosomal recessive lysosomal storage disorder (LSD) due to mutations which cause absent or deficient activity of the enzyme acid α-glucosidase (GAA). Depending on age of onset, organ involvement, and rate of progression, PD can be classified as an Infantile-onset form (IOPD) with severe phenotype and rapid disease progression and a Late-onset form (LOPD), characterized by a clinical spectrum that includes myopathy and respiratory impairment. Typical histopathological findings reveal a vacuolar myopathy due to glycogen accumulation within lysosomes and dysfunctional autophagic activity. Diagnosis of PD could be confirmed preliminary by Dried Blood Spot (DBS) that measures GAA activity, followed by GAA genetic analysis. Enzyme replacement therapy (ERT) modified the natural history of PD, but its effects in LOPD patients are limited, particularly in terms of musculoskeletal involvement. Indeed, it is recommended to monitor all PD patients with instrumental and laboratory studies of bone and muscle health. As a component of interdisciplinary management of PD, rehabilitation is a mainstay because of its benefits on functional independence, social participation and quality of life, by prescribing physical activity and tailored therapeutic exercise.