Genetics of Pompe Disease: The secrets within the coding region of the GAA gene and beyond

The main subject addressed in this thesis is the genotype-phenotype relationship in Pompe disease. Pompe disease is a rare, autosomal recessive disorder caused by disease-associated variants (mutations) in the gene coding for the enzyme acid-α-glucosidase (GAA). The function of GAA is to degrade glycogen to glucose in the lysosome. Deficiency of GAA will result in glycogen accumulation in the lysosome, causing damage to the cells and tissues, leading to loss of function. The research described in this thesis could define the best methods and samples of diagnosing Pompe disease enzymatically. Moreover, molecular analysis is an essential step to conclude the diagnostic procedure of a Pompe patient. The results showed the need for additional analyses to detect new disease-associated GAA variants when conventional methods are insufficient. Furthermore, most of the work showed and discussed in this thesis explores the genotype-phenotype correlation in Pompe disease