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Late onset Pompe disease: benefits of identifying Pompe patients and the role of the enzyme replacement therapy. Review of two recent papers in Neuromuscular Disorders

Commentary by Maria Fuller:
Pompe disease, also known as glycogen storage disease type II, is an inherited, progressive form of muscular dystrophy caused by a deficiency of the lysosomal enzyme, acid alpha-glucosidase. Consequently, the substrate for this enzyme, glycogen, accumulates in the lysosomes of affected cells, primarily in skeletal and cardiac muscle. Two main clinical forms of Pompe disease are recognized: an infantile and later onset form differentiated based on age of clinical presentation and phenotype.

Progressive limb girdle muscle weakness is characteristic of the late onset form and Lee et al embarked on a screening study to identify late onset Pompe disease patients in a targeted, select Korean population. Alpha-glucosidase was measured in 90 individuals with clinically diagnosed myopathy and 16 individuals demonstrated reduced activity. Of these, two were confirmed late onset Pompe patients by mutations with the remainder carrying at least one pseudo-deficiency allele. The frequency of Pompe disease in this cohort was estimated at 2.2%.

One of the major benefits of identifying Pompe patients is that treatment, in the form of enzyme replacement therapy, is available. To this end, the Sechi et al. investigated the impact of enzyme replacement therapy on muscle performance in late onset Pompe patients. Although numbers were small – six female and five male Pompe patients – all patients failed to show an immediate effect on exercise tolerance with enzyme replacement therapy. This is most likely explained by the differences in mobilisation of glycogen from the lysosomal compartment compared with cytoplasmic stores, the latter required when demand for glucose is high during exercise. Enzyme replacement with acid alpha-glucosidase will facilitate break down of lysosomal glycogen but has no impact on cytoplasmic glycogen. Therefore, the benefit of enzyme replacement therapy for Pompe patients is derived from the improvement on muscle function that occurs from long term, continuous exposure of muscle cells to acid alpha-glucosidase preventing the relentless buildup of lysosomal glycogen.

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About the journal

Molecular Genetics and Metabolism is a contribution to the understanding of the metabolic basis of disease. The journal publishes articles describing investigations that use the tools of biochemistry and molecular biology for studies of normal and diseased states. In addition to original research articles, occasional minireviews reporting timely advances as well as brief communications and letters to the editor are considered.

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