Two mutations affecting the transport and maturation of lysosomal alpha-glucosidase in an adult case of glycogen storage disease type II.

The autosomal recessive glycogen storage disease type II is associated with a deficiency of lysosomal alpha-glucosidase (acid maltase). This paper reports on the mutations in the lysosomal alpha-glucosidase alleles of an adult patient. A G-1927 to A transition was discovered in exon 14 causing the substitution of Gly-643 by Arg and a second C-2173 to T transition in exon 15 resulting in the substitution of Arg-725 by Trp. Each of the mutations was located in a different allele. The mutations were introduced in the wild-type lysosomal alpha-glucosidase cDNA and expressed in COS cells. Both mutations had a similar effect. The synthesis of the mutant enzyme precursors was not disturbed but the intracellular transport and maturation were impaired. As a result there was an overall deficiency of catalytic activity.