Two mutations affecting the transport and maturation of lysosomal α‐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 α‐glucosidase (acid maltase). This paper reports on the mutations in the lysosomal α‐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 α‐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. © 1993 Wiley‐Liss, Inc.