• glycogen storage disease type II (GSDII);
  • Pompe disease;
  • acid α-glucosidase gene;
  • splicing mutation;
  • genotype–phenotype correlations


Glycogen storage disease type II (GSDII) results from deleterious mutations in acid α-glucosidase gene. To date several mutant alleles have been studied including missense and nonsense mutations, insertions, small and large deletions as well as splice site mutations. Apart from IVS1 (− 13[RIGHTWARDS ARROW]G), 525delT, and Δ18, the other mutations are rare and often unique to single patients. Moreover, the molecular findings also observed in the different ethnic groups makes it difficult to attempt to correlate genotype and phenotype to explain the origin of clinical variability. Even though there are no conclusive genotype phenotype correlations, the in frame splice site mutations identified up until now have been found associated with the juvenile/adult onset of GSDII. In this study we describe a novel in frame splicing defect, IVS9 (+2GT[RIGHTWARDS ARROW]GC), identified in combination with the rare IVS10 (+1GT[RIGHTWARDS ARROW]CT) mutation in a patient with classic infantile GSDII disease. Because both mutations occur at the catalytic site region, it is likely that the alteration of both catalytic function and steric conformation of the enzyme may be responsible for the most severe form of the disease. © 2001 Wiley-Liss, Inc.