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

Authors

  • Deeksha S. Bali PhD,

    Corresponding author
    1. Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, 801 Capitola Drive, Suite 6, Durham, North Carolina 27713, USA
    • Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, 801 Capitola Drive, Suite 6, Durham, North Carolina 27713, USA
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    • Disclosure: P.S.K. and D.S.B. have received research/grant support and honoraria from Genzyme Corporation. P.S.K. is a member of the Pompe and Gaucher Disease Registry Advisory Board for Genzyme Corporation. Recombinant human GAA (rhGAA), in the form of Genzyme's product alglucosidase alfa (Myozyme/Lumizyme) has been approved by the U.S. FDA and the European Union as therapy for Pompe disease. Duke University and those who invented this method of treatment and predecessors of the cell lines used to generate the enzyme (rhGAA) receive royalty payments pursuant to the University's Policy on Inventions, Patents and Technology Transfer.

  • Adviye A. Tolun MS, PhD,

    1. Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, 801 Capitola Drive, Suite 6, Durham, North Carolina 27713, USA
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    • Disclosure: P.S.K. and D.S.B. have received research/grant support and honoraria from Genzyme Corporation. P.S.K. is a member of the Pompe and Gaucher Disease Registry Advisory Board for Genzyme Corporation. Recombinant human GAA (rhGAA), in the form of Genzyme's product alglucosidase alfa (Myozyme/Lumizyme) has been approved by the U.S. FDA and the European Union as therapy for Pompe disease. Duke University and those who invented this method of treatment and predecessors of the cell lines used to generate the enzyme (rhGAA) receive royalty payments pursuant to the University's Policy on Inventions, Patents and Technology Transfer.

  • Jennifer L. Goldstein PhD, MS,

    1. Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, 801 Capitola Drive, Suite 6, Durham, North Carolina 27713, USA
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    • Disclosure: P.S.K. and D.S.B. have received research/grant support and honoraria from Genzyme Corporation. P.S.K. is a member of the Pompe and Gaucher Disease Registry Advisory Board for Genzyme Corporation. Recombinant human GAA (rhGAA), in the form of Genzyme's product alglucosidase alfa (Myozyme/Lumizyme) has been approved by the U.S. FDA and the European Union as therapy for Pompe disease. Duke University and those who invented this method of treatment and predecessors of the cell lines used to generate the enzyme (rhGAA) receive royalty payments pursuant to the University's Policy on Inventions, Patents and Technology Transfer.

  • Jian Dai BS,

    1. Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, 801 Capitola Drive, Suite 6, Durham, North Carolina 27713, USA
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    • Disclosure: P.S.K. and D.S.B. have received research/grant support and honoraria from Genzyme Corporation. P.S.K. is a member of the Pompe and Gaucher Disease Registry Advisory Board for Genzyme Corporation. Recombinant human GAA (rhGAA), in the form of Genzyme's product alglucosidase alfa (Myozyme/Lumizyme) has been approved by the U.S. FDA and the European Union as therapy for Pompe disease. Duke University and those who invented this method of treatment and predecessors of the cell lines used to generate the enzyme (rhGAA) receive royalty payments pursuant to the University's Policy on Inventions, Patents and Technology Transfer.

  • Priya S. Kishnani MD

    1. Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, 801 Capitola Drive, Suite 6, Durham, North Carolina 27713, USA
    Search for more papers by this author
    • Disclosure: P.S.K. and D.S.B. have received research/grant support and honoraria from Genzyme Corporation. P.S.K. is a member of the Pompe and Gaucher Disease Registry Advisory Board for Genzyme Corporation. Recombinant human GAA (rhGAA), in the form of Genzyme's product alglucosidase alfa (Myozyme/Lumizyme) has been approved by the U.S. FDA and the European Union as therapy for Pompe disease. Duke University and those who invented this method of treatment and predecessors of the cell lines used to generate the enzyme (rhGAA) receive royalty payments pursuant to the University's Policy on Inventions, Patents and Technology Transfer.


Abstract

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. Muscle Nerve, 2011

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