Background: Pompe disease is an autosomal recessive disorder of glycogen metabolism resulting from a deficiency of acid alpha-glucosidase. Pompe disease can present within a broad clinical spectrum, from the severe infantile to the attenuated adult onset phenotypes. Early diagnosis, in the form of newborn screening has been proposed. However, in the absence of clinical symptoms, prediction of disease severity and progression will be critical to provide appropriate management and treatment of affected individuals.
Methods: We have used sensitive immune-assays to measure levels of acid alpha-glucosidase protein and activity in cultured skin fibroblasts and a new glycogen assay to specifically determine the lysosomal accumulation of glycogen in the same cells. These markers were assessed for their ability to predict age of onset.
Results: Acid alpha-glucosidase activity and specific activity as well as lysosomal glycogen showed significant correlations with age of onset, with acid alpha-glucosidase activity having the highest Spearman correlation coefficient (0.887, p<0.001). Lysosomal glycogen accumulated only in cells from infantile and juvenile patients but not from adult-onset patients. However, cells from adult-onset patients had relatively low cytoplasmic glycogen compared to control individuals and other forms of the disease.
Conclusion: Acid-alpha-glucosidase activity and specific activity, and lysosomal glycogen content are useful predictors of age of onset in Pompe disease.