Pompe disease is a rare autosomal recessive disease with an estimated incidence of 1:40,000 live births.
PD is due to mutations of the acid α-glucosidase (GAA) gene, encoding the lysosomal hydrolase α-glucosidase (acid maltase, GAA, E.C.3.2.1.20). GAA deficiency results in generalized tissue glycogen accumulation and secondary cardiac and skeletal muscle destruction (Figure 1).

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Figure 1. The enzyme acid alpha-glucosidase (GAA) breaks down glycogen inside the subcellular compartments called lysosomes (top). In Pompe’s disease, a deficiency of GAA causes glycogen to accumulate and rupture lysosomes (middle). In enzyme replacement therapy (ERT), intravenously injected GAA is taken up by lysosomes that have fused with the cell’s outer surface, eventually making its way to glycogen-filled lysosomes (bottom).

Different mutations of the GAA gene result in a wide phenotypic variability, ranging from the devastating classic infantile form, characterized by early onset, severe hypertrophic cardiomyopathy, marked hypotonia, hepatomegaly, and invariably fatal outcome by one year of age, to the late onset childhood, juvenile or adult forms, characterized by skeletal myopathy, in the absence of cardiac disease. Infantile onset non-classic phenotypes have been described, presenting within the first two years of life, with milder or absent heart involvement.

Recent studies performed in a mouse model of PD have suggested that impairment of autophagy is implicated in muscle cell damage. The prominent muscular involvement makes Pompe disease an example of a metabolic myopathy. Therapeutic intervention should be aimed at reverting cardiac and muscular manifestations of the disease.

ERT with recombinant human GAA (rhGAA) derived from either rabbit milk or Chinese Hamster Ovary (CHO) cells has been recently introduced in the treatment of PD patients (Figure 1). The results support the effectiveness of ERT on cardiomyopathy and motor function in the classic infantile PD patients, whereas the effects of ERT on skeletal myopathy in the late-onset patients are variable.
These observations suggest that a search for alternative therapeutic approaches to PD, other than ERT, is warranted, particularly for patients with late-onset forms and prominent skeletal muscle disease.

More information at:
Wikipedia
National Institute of Neurological Disorders and Stroke
Genetics Home Reference

Patient organizations:
Acid Maltase Deficiency Association
International Pompe Association
Pompe Center ErasmusMC Rotterdam (Partner 3 website)