MOLECULAR ANALYSIS AND PROTEIN PROCESSING IN LATE-ONSET POMPE DISEASE PATIENTS WITH LOW LEVELS OF ACID α-GLUCOSIDASE ACTIVITY

Introduction: Pompe disease (glycogen storage disease type II, acid maltase deficiency) is caused by deficiency of lysosomal acid alpha-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. Muscle Nerve 43: 665-670, 2011