S1.3 Adult-onset Pompe disease

Clinical diversity is a common phenomenon in lysosomal storage diseases and has led to the introduction of clinical subtypes. The natural course of Pompe disease is primarily dictated by the type of mutations in the acid alpha-glucosidase gene (GAA) or rather by the residual enzyme activity of acid alphaglucosidase resulting from the combination of the mutated allelic products. Thirty per cent of normal acid-alpha-glucosidase activity in skeletal muscle is the critical threshold below which lysosomal glycogen storage starts and disease symptoms manifest. Patients with late onset Pompe disease generally have more acid-alpha-glucosidase activity in muscle cells and/or fibroblasts than severely affected infants with classic infantile Pompe disease. These latter never have more than 2% of normal acidalpha-glucosidase activity. The so-called adult form of Pompe disease is not an autonomous entity with respect to the classic and juvenile ones, but differs from them mainly for the lower speed of accumulation of glycogen within the lysosomes which explains the late onset of skeletal muscle tissue changes and clinical manifestations.