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 infa ntile glycogen storage disease type II (GSD II) and virtual absence of acid alpha-glucosidase activity in leukocytes and cultured skin fibro blasts. The patients were identified as homozygotes for a deletion of exon 18 of the acid alpha-glucosidase gene (GAA), The in-frame deletio n manifests at the protein level in a characteristic way: the enzyme p recursor is smaller than normal and degraded in the endoplasmic reticu lum or Golgi complex. These cases present an evident example of a geno type-phenotype correlation in glycogen storage disease type II.