Glycogenosis type II (acid maltase deficiency)

Abstract

Glycogen storage disease type II (GSD II/glycogenosis type II/Pompe's disease/acid maltase deficiency) is caused by the deficiency of lysosomal α‐glucosidase resulting in lysosomal accumulation of glycogen. The disease is inherited as an autosomal recessive trait and is clinically heterogeneous. Early and late onset phenotypes are distinguished. Insight in the molecular nature of the lysosomal α‐glucosidase deficiency and the underlying genetic defect has increased significantly during the past decade. This minireview on GSD II was written at the occasion of The International Symposium on Glycolytic and Mitochondrial Defects in Muscle and Nerve, held in Osaka, Japan, July 1994. It is an update of current literature, but also includes original data from the collaborating authors on mutations occurring in the lysosomal α‐glucosidase gene and on prenatal diagnosis by chorionic villus sampling. The genotype–phenotype correlation and the prospects for therapy are addressed. © 1995 John Wiley & Sons, Inc.

Improved efficacy of gene therapy approaches for Pompe disease using a new, immune-deficient GSD-II mouse model

“…These patients eventually succumb to the multiple morbidities associated with respiratory insufficiency/failure. 4,5 To combat this devastating disease enzyme replacement therapy (ERT) attempts, using recombinant human acid-alpha glucosidase (rhGAA) produced from either transgenic rabbit milk 6,7 or Chinese hamster ovary rGAA producer cell lines, 8 have demonstrated promising results, with most of the infantile GSD-II patients treated in these trials surviving past the milestone of 1 year. However, the ERT approach is limited by the difficulties of large-scale enzyme production, and the need for repetitive, life-long enzyme injections.…”

Frequency of glycogen storage disease type II in The Netherlands: implications for diagnosis and genetic counselling

“…Late-onset GSD II is clinically very heterogeneous, and presents at juvenile age to late adulthood as a slowly progressive proximal myopathy. 2 The prospect of enzyme therapy for GSD II highlights the immediate need for accurate figures on the frequency of the disease. 3,4 The figure of 1 in 100 000 normally quoted is not based on solid data.…”

“…3,4 The figure of 1 in 100 000 normally quoted is not based on solid data. 1,5 Given present knowledge of the molecular genetics of GSD II, 1,2,6 and the genotype-phenotype correlation, 7,8 we now have the tools to update the meagre and aging data on the frequency of the disease. In order to determine the frequency of GSD II we screened a random sample of newborns for three frequent mutations in the acid α-glucosidase gene.…”

Complete correction of acid α-glucosidase deficiency in Pompe disease fibroblasts in vitro, and lysosomally targeted expression in neonatal rat cardiac and skeletal muscle

“…1 Partial restoration of acid ␣-glucosidase (Ad-GAA) activity in affected organs to 20-30% of the wildtype activity would, in principle, constitute an effective treatment. 1,5 In human cells, a 3.4-to 3.6-kb acid ␣-glucosidase mRNA 6 is transcribed to produce a 105-to 110-kDa pre-cursor protein that is cotranslationally inserted into the endoplasmic reticulum. 7 Subsequent modification of Nlinked sugar residues by the addition of mannose 6-phosphate targets newly synthesized enzyme to the lysosomal compartment.…”