Pompe Disease

Pompe disease is an autosomal recessive genetic disorder caused by a deficiency or dysfunction of the lysosomal hydrolase acid alpha-glucosidase (GAA). This enzymatic defect results in lysosomal glycogen accumulation in multiple tissues, with cardiac and skeletal muscle tissues most seriously affected. In the fatal infantile-onset form, the disease presents rapidly with hypotonia, generalized muscle weakness, and hypertrophic cardiomyopathy. Death usually occurs within one year of birth due to cardiorespiratory failure. ^{[1, 2]}

The image on the left depicts a normal muscle cell, while the image on the right illustrates what may happen in Pompe disease. As glycogen accumulates in affected cells, it may cause the lysosomes to enlarge, eventually impairing muscle function.

The late-onset form of Pompe disease, which was discovered more than 30 years after the infantile-onset form, is more clinically heterogeneous, with greater variation in age of symptom onset, clinical presentation, and disease progression. Late-onset patients may have residual GAA activity less than 40% of normal when measured in skin fibroblasts^[3]. Generally characterized by slowly progressive proximal muscle weakness and respiratory insufficiency, this form can present anytime from childhood until adulthood. It is distinguished from the infantile-onset form by the absence of severe cardiac involvement. While life expectancy can vary, death generally occurs due to respiratory failure.^[4]

References

1. Hirschhorn, Rochelle and Arnold J. J. Reuser. Glycogen Storage Disease Type II: Acid Alpha-glucosidase (Acid Maltase) Deficiency. In: Scriver C, Beaudet A, Sly W, Valle D, eds. The Metabolic and Molecular Bases of Inherited Disease. 8th Edition. New York: McGraw-Hill, 2001. 3389-3420.

2 . Slonim AE, Bulone L, Ritz S et al. Identification of two subtypes of infantile acid maltase deficiency. J Pediatr 2000 Aug;137(2):283-5.

3 Chen YT, Amalfitano A. Towards a molecular therapy for glycogen storage disease type II (Pompe disease). Mol Med Today 2000 Jun; 6(6): 245-51.

4 Hirschhorn, Rochelle and Arnold J. J. Reuser. Glycogen Storage Disease Type II: Acid Alpha-glucosidase (Acid Maltase) Deficiency. In: Scriver C, Beaudet A, Sly W, Valle D, eds. The Metabolic and Molecular Bases of Inherited Disease. 8th Edition. New York: McGraw-Hill, 2001. 3389-3420.