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


Dept. of Clinical Genetics, Erasmus University, P.O. Box 1738, 3000 OR Rotterdam, The Netherlands Tel:-31-10-408.7153 Fax:-31-10-436.2536


We describe two unrelated Dutch patients with typical symptoms of infantile glycogen storage disease type II (GSD II) and virtual absence of acid α-glucosidase activity in leukocytes and cultured skin fibroblasts. The patients were identified as homozygotes for a deletion of exon 18 of the acid α-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 cases present an evident example of a genotype-phenotype correlation in glycogen storage disease type II.