Glycogen storage disease type II (GSD II) is an autosomal recessive myopathy. Early and lateonset phenotypes are distinguished -infantile, juvenile and adult. Three mutations in the acid α-glucosidase gene are common in the Dutch patient population: IVS1(-13T→G), 525delT and delexon18. 63% of Dutch GSD II patients carry one or two of these mutations, and the genotype-phenotype correlation is known. To determine the frequency of GSD II, we have screened an unselected sample of neonates for the occurrence of these three mutations. Based on the calculated carrier frequencies, the predicted frequency of the disease is 1 in 40 000 divided by 1 in 138 000 for infantile GSD II and 1 in 57 000 for adult GSD II. This is about two to four times higher than previously suggested, which is a reason to become more familiar with the presentation of GSD II in its different clinical forms and to adjust the risk assessment for genetic counselling.

In nine Dutch patients with the infantile form of glycogen storage disease type II (GSDII), who were compound heterozygous for either 525delT or exon18del (1), sequence analysis was performed to search for the mutations in the second lysosomal a‐glucosidase allele. One patient had a novel TG deletion at cDNA position 379 + 380. Surprisingly five of the nine patients had the same two base pair changes: A921 ± T and G925 ±A. The first change is a well‐known polymorphism but the second one is a novel mutation and results in the substitution of Gly309 by Arg. By screening 43 other GSDII patients the same mutation was found in two other cases, one from The Netherlands and one from France. To verify its deleterious effect, the mutation was introduced in the wild type lysosomal α‐glucosidase cDNA and expressed in COS cells.