Pompe disease: pathogenesis, molecular genetics and diagnosis

Pompe disease (PD) is a rare autosomal recessive disorder caused by mutations in the GAA gene, localized onchromosome 17 and encoding for acid alpha-1,4-glucosidase (GAA). Currently, more than 560 mutations spreadthroughout GAA gene have been reported. GAA catalyzes the hydrolysis of ?-1,4 and ?-1,6-glucosidic bonds ofglycogen and its deficiency leads to lysosomal storage of glycogen in several tissues, particularly in muscle. PD isa chronic and progressive pathology usually characterized by limb-girdle muscle weakness and respiratoryfailure. PD is classified as infantile and childhood/adult forms. PD patients exhibit a multisystemicmanifestation that depends on age of onset.Early diagnosis is essential to prevent or reduce the irreversible organ damage associated with PD progression.Here, we make an overview of PD focusing on pathogenesis, clinical phenotypes, molecular genetics, diagnosis,therapies, autophagy and the role of miRNAs as potential biomarkers for PD.