Molecular analysis and protein processing in late-onset Pompe disease patients with low levels of acid α-glucosidase activity.

Journal Article (Journal Article)

INTRODUCTION: Pompe disease (glycogen storage disease type II, acid maltase deficiency) is caused by deficiency of lysosomal acid α-glucosidase (GAA). A few late-onset patients have been reported with skin fibroblast GAA activity levels of <2%. METHODS: We measured GAA activity in skin fibroblasts from 101 patients with late-onset Pompe disease. Whenever possible, we performed Western blot analysis and correlated the results with GAA activity and GAA gene mutations. RESULTS: Thirteen patients (13%) had skin fibroblast GAA activity of <1% of normal. Although there was wide genetic heterogeneity, none of these patients carried the common late-onset mutation c.-32-13T > G. We performed Western blot on 11 patients with <1% GAA activity. All produced GAA protein that was at lower levels and/or was abnormally processed. DISCUSSION: There is no common mutation associated with <1% GAA activity in late-onset Pompe disease patients. Most patients produce unprocessed forms of GAA protein compared with patients with higher GAA activity.

Full Text

Duke Authors

Cited Authors

  • Bali, DS; Tolun, AA; Goldstein, JL; Dai, J; Kishnani, PS

Published Date

  • May 2011

Published In

Volume / Issue

  • 43 / 5

Start / End Page

  • 665 - 670

PubMed ID

  • 21484825

Electronic International Standard Serial Number (EISSN)

  • 1097-4598

Digital Object Identifier (DOI)

  • 10.1002/mus.21933


  • eng

Conference Location

  • United States