Homozygous deletion of exon 18 leads to degradation of the lysosomal alpha-glucosidase precursor and to the infantile form of glycogen storage disease type II.

We describe two unrelated Dutch patients with typical symptoms of infantile glycogen storage disease type II (GSD II) and virtual absence of acid alpha-glucosidase activity in leukocytes and cultured skin fibroblasts. The patients were identified as homozygotes for a deletion of exon 18 of the acid alpha-glucosidase gene (GAA). The in-frame deletion manifests at the protein level in a characteristic way: the enzyme precursor is smaller than normal and degraded in the endoplasmic reticulum or Golgi complex. These case present an evident example of a genotype-phenotype correlation in glycogen storage disease type II.