The impact of Pompe disease on smooth muscle: a review

Abstract

Pompe disease (OMIM 232300) is an autosomal recessive disorder caused by mutations in the gene encoding acid α-glucosidase (GAA) (EC 3.2.1.20), the enzyme responsible for hydrolyzing lysosomal glycogen. The primary cellular pathology is lysosomal glycogen accumulation in cardiac muscle, skeletal muscle, and motor neurons, which ultimately results in cardiorespiratory failure. However, the severity of pathology and its impact on clinical outcomes are poorly described in smooth muscle. The advent of enzyme replacement therapy (ERT) in 2006 has improved clinical outcomes in infantile-onset Pompe disease patients. Although ERT increases patient life expectancy and ventilator free survival, it is not entirely curative. Persistent motor neuron pathology and weakness of respiratory muscles, including airway smooth muscles, contribute to the need for mechanical ventilation by some patients on ERT. Some patients on ERT continue to experience life-threatening pathology to vascular smooth muscle, such as aneurysms or dissections within the aorta and cerebral arteries. Better characterization of the disease impact on smooth muscle will inform treatment development and help anticipate later complications. This review summarizes the published knowledge of smooth muscle pathology associated with Pompe disease in animal models and in patients.

Keywords: Pompe disease; airway; gastrointestinal; smooth muscle; vasculature.

Fig. 1.

Glycogen Deposits found within Airway Smooth Muscle of Gaa^−/− Mouse. Representative images of fixed and plastic embedded tissue, sectioned, and stained with Periodic Acid-Schiff reagents to detect glycogen, then counterstained with Toluidine Blue. 2μm sections from the trachealis of six-month-old (A) wildtype and (B) Gaa^−/− mice are indicative of the smooth muscle found along the airway musculature. Aggregates of pink puncta indicate large deposits of glycogen within lysosomes. Scale bar = 20 μm.

Fig. 2.

Glycogen Deposits found within Vascular, GI, and GU Smooth Muscle of Gaa^−/− Mouse. Representative images of fixed and plastic embedded tissue, sectioned to, and stained with Periodic Acid-Schiff reagents to detect glycogen, then counterstained with Toluidine Blue. 2μm sections from the esophagus of six-month-old (A and C) wildtype and (B and D) Gaa^−/− mice are indicative of the smooth muscle found along the vascular system (A and B) as well as within the gastrointestinal tract (C and D). 2μm sections from the bladder of (E) wildtype and (F) Gaa^−/− mice represent the pathology present in the genitourinary. Aggregates of pink puncta indicate large deposits of glycogen within lysosomes. Scale bar = 20 μm.