Glycogen storage disease type II (GSDII; Pompe disease or acid maltase 
deficiency) is an autosomal recessive disorder caused by lysosomal acid 
alpha-glucosidase (AalphaGlu) deficiency and manifests predominantly as skeletal 
muscle weakness. Defects in post-translational modification and transport of 
mutant AalphaGlu species are frequently encountered and may potentially be 
corrected with chaperone-mediated therapy. In the present study, we have tested 
this hypothesis by using deoxynojirimycin and derivatives as chemical chaperones 
to correct the AalphaGlu deficiency in cultured fibroblasts from patients with 
GSDII. Four mutant phenotypes were chosen: Y455F/Y455F, P545L/P545L, 
525del/R600C and D645E/R854X. In case of Y455F/Y455F and P545L/P545L, 
N-(n-butyl)deoxynojirimycin (NB-DNJ) restored the transport, maturation and 
activity of AalphaGlu in a dose dependent manner, while it had no effect on the 
reference enzyme beta-hexosaminidase. NB-DNJ promoted export from the 
endoplasmic reticulum (ER) to the lysosomes and stabilized the activity of 
mutant AalphaGlu species, Y455F and P545L, inside the lysosomes. In long-term 
culture, the AalphaGlu activity in the fibroblasts from the patients with mutant 
phenotypes, Y455F/Y455F and P545L/P545L, increased up to 14.0- and 7.9-fold, 
respectively, in the presence of 10mumol/L NB-DNJ. However, the effect of NB-DNJ 
on Y455F/Y455F subsided quickly after removal of the compound. We conclude that 
NB-DNJ acts in low concentration as chemical chaperone for certain mutant forms 
of AalphaGlu that are trapped in the ER, poorly transported or labile in the 
lysosomal environment. Chemical chaperone therapy could create new perspectives 
for therapeutic intervention in GSDII.