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Molecular analysis and protein processing in late‐onset pompe disease patients with low levels of acid α‐glucosidase activity
Author(s) -
Bali Deeksha S.,
Tolun Adviye A.,
Goldstein Jennifer L.,
Dai Jian,
Kishnani Priya S.
Publication year - 2011
Publication title -
muscle and nerve
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.025
H-Index - 145
eISSN - 1097-4598
pISSN - 0148-639X
DOI - 10.1002/mus.21933
Subject(s) - disease , medicine , glycogen storage disease type ii , enzyme replacement therapy , biochemistry , endocrinology , chemistry
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. Muscle Nerve, 2011