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Fractures in children with Pompe disease: a potentiallong-term complication

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Abstract

Background

Pompe disease (glycogen storage disease type II or acid maltase deficiency) is an autosomal recessive disorder caused by deficiency of the lysosomal enzyme acid α-glucosidase (GAA). Classic infantile-onset disease, characterized by cardiomegaly and profound weakness, leads to death in the first year of life from cardiorespiratory failure. Reversal of cardiomyopathy and improved motor function have been shown in clinical trials of rhGAA enzyme replacement therapy (ERT) with alglucosidase alfa (Myozyme), recently approved for clinical use. Increased survival potentially unmasks long-term complications of this previously lethal disease, including risk of skeletal fracture, recently identified at our institution and not previously reported in children with Pompe disease.

Objective

To report the risk of fracture in children with Pompe disease with increased survival with ERT.

Materials and methods

We present four cases of fracture in patients with classic infantile Pompe disease treated with ERT at our institution, and review a study database for additional reports of fracture in this population.

Results

We review 19 fractures in 14 children with Pompe disease on ERT.

Conclusion

Radiologists should be familiar with and vigilant for the association of fractures and increased survival on ERT in children with Pompe disease. We discuss potential mechanisms, implications for radiographic surveillance, potential intervention, and needs for further research.

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Financial disclosures

The clinical trials with rhGAA were supported by grants from Genzyme Corporation at the various sites that patients were treated. P.S.K. has received research/grant support and honoraria from Genzyme Corporation. P.S.K. is a member of the Pompe Disease Advisory Board for Genzyme Corporation. L.E.C. has received honoraria from Genzyme Corporation and research support from the Leal Foundation. S.D. and J.M. have received honoraria from Genzyme Corporation. Y.T.C. has served as a consultant for Genzyme Corporation. rhGAA, in the form of Genzyme’s product, Myozyme, has now been approved by the US FDA and the European Union as therapy for Pompe disease. Duke University and inventors of the method of treatment and predecessors of the cell lines used to generate the enzyme (rhGAA) used in the clinical trials could benefit financially pursuant to the University’s Policy on Inventions Patents and Technology.

Author information

Authors and Affiliations

  1. Division of Physical Therapy, Department of Community and Family Medicine, Duke University Medical Center, Durham, NC, USA

    Laura E. Case

  2. Department of Pediatrics, Duke University Medical Center, Durham, NC, 27710, USA

    Rabi Hanna, Stephanie DeArmey, Joanne Mackey, Anne Boney, Yuan-Tsong Chen & Priya S. Kishnani

  3. Department of Radiology, Duke University Medical Center, Durham, NC, USA

    Donald P. Frush

  4. Pharmacovigilance, Genzyme Corporation, Cambridge, MA, USA

    Claire Morgan & Susan Bouchard

  5. Genzyme Corporation, Cambridge, MA, USA

    Deyanira Corzo

  6. Department of Medicine, Duke University Medical Center, Durham, NC, USA

    Thomas J. Weber

  7. Department of Pediatrics and Department of Medicine, Duke University Medical Center, Durham, NC, 27710, USA

    Vidya Krishnamurthy

Authors
  1. Laura E. Case
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  2. Rabi Hanna
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  3. Donald P. Frush
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  4. Vidya Krishnamurthy
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  5. Stephanie DeArmey
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  6. Joanne Mackey
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  7. Anne Boney
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  8. Claire Morgan
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  9. Deyanira Corzo
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  10. Susan Bouchard
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  11. Thomas J. Weber
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  12. Yuan-Tsong Chen
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  13. Priya S. Kishnani
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Corresponding author

Correspondence to Priya S. Kishnani.

Additional information

Laura E. Case and Rabi Hanna contributed equally to this study.

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Case, L.E., Hanna, R., Frush, D.P. et al. Fractures in children with Pompe disease: a potentiallong-term complication. Pediatr Radiol 37, 437–445 (2007). https://doi.org/10.1007/s00247-007-0428-y

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  • DOI: https://doi.org/10.1007/s00247-007-0428-y

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