Background: Glycogenosis type II or Pompe disease is an autosomal-recessive lysosomal storage disease due to mutations in the gene encoding acid alpha-glucosidase (GAA), an enzyme required for lysosomal glycogen degradation. The disease predominantly affects the skeletal and respiratory muscles but there is growing evidence of the involvement of smooth muscle cells in blood vessel walls, suggesting a multi-system disorder. Moreover, the failure of autophagy in Pompe disease could contribute to muscular atrophy and disease progression and is thought to compromise the efficacy of enzyme replacement therapy (ERT).
Methods: We investigated the light microscopical and ultrastructural pathology of the arrector pili muscle from punch skin biopsies from the calf of 6 adult Pompe disease patients and 6 age and gender matched healthy controls. Two patients had a follow-up biopsy after 19 and 20 month of ERT.
Results: The electron microscopic investigation of patient biopsies revealed the widespread occurrence of glycogenosomes, membrane bound accumulations of granular glycogen, associated with autophagic vacuoles. In the controls we detected only muscle cells with non-membrane bound forms of glycogen. These morphological changes in smooth muscle cells are similar to those seen in skeletal muscle and smooth muscle cells of arterioles of Pompe patients. Furthermore, two patients with pre- and post-ERT skin biopsies showed a decrease in the number of cells with extensive autophagy after treatment.
Conclusions: Electron microscopic examination of the arrector pili muscles appears to be a surrogate marker for the involvement of smooth muscles reflecting disease severity. These findings suggest that the standardized and widely used skin biopsy could offer a minimally invasive way to screen for smooth muscle involvement and warrant further studies in larger cohorts of patients.