2 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 all eles of an adult patient. A G-1927 to A transition was discovered in e xon 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 mut ations were introduced in the wild-type lysosomal alpha-glucosidase cD NA and expressed in COS cells. Both mutations had a similar effect. Th e synthesis of the mutant enzyme precursors was not disturbed but the intracellular transport and maturation were impaired. As a result ther e was an overall deficiency of catalytic activity. (C) 1993 Wiley-Liss , Inc.