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CRIM-negative infantile Pompe disease: 42-month treatment outcome

  • Original Article
  • Published:
Journal of Inherited Metabolic Disease

Abstract

Pompe disease is a rare lysosomal glycogen storage disorder characterized by deficiency of acid α-glucosidase enzyme (GAA) and caused by mutations in the GAA gene. Infantile-type Pompe disease is a multiorgan disorder presenting with cardiomyopathy, hypotonia, and muscular weakness, which is usually fatal. Enzyme replacement therapy (ERT) with recombinant human GAA (rhGAA) has recently been shown to be effective and subsequently yielded promising results in cross-reactive immunologic material (CRIM)-positive patients. CRIM-negative patients showed a limited response to ERT and died or were ventilator dependant. Over a period of 44 months, we monitored cognitive and motor development, behavior, auditory function, and brain imaging of a CRIM-negative infantile Pompe disease patient on rhGAA and monoclonal anti-immunoglobulin E (anti-IgE) antibody (omalizumab) treatment due to severe allergic reaction. Cardiorespiratory and skeletal muscle response was significant, with almost normal motor development. Cognitive development—in particular, speech and language—deviated increasingly from normal age-appropriate development and was markedly delayed at 44 months, unexplained by moderate sensorineural hearing impairment. Brain magnetic resonance imaging (MRI) at 18, 30, and 44 months of age revealed symmetrical signal alteration of the deep white matter. Titer values of IgG antibodies to rhGAA always remained <1:800. The potential role of omalizumab in immune modulation remains to be elucidated; however, this is the first report presenting a ventilator-free survival of a CRIM-negative patient beyond the age of 36 months. The central nervous system (CNS) findings are hypothesized to be part of a yet not fully described CNS phenotype in treated patients with longer survival.

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Fig. 1

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Abbreviations

ERT:

enzyme replacement therapy

MRI:

magnetic resonance imaging

CNS:

central nervous system

GAA:

acid α-glucosidase

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Authors and Affiliations

  1. Division of Metabolism, University Children’s Hospital Zürich, Steinwiesstrasse 75, 8032, Zürich, Switzerland

    Marianne Rohrbach & Matthias R. Baumgartner

  2. Division of Neurology, University Children’s Hospital Zürich, Zürich, Switzerland

    Andrea Klein

  3. Division of Allergy, University Children’s Hospital Zürich, Zürich, Switzerland

    Alice Köhli-Wiesner & Roger Lauener

  4. Division of Otorhinolaryngology, University Children’s Hospital Zürich, Zürich, Switzerland

    Dorothe Veraguth

  5. Division of Radiology, University Children’s Hospital Zürich, Zürich, Switzerland

    Ianina Scheer

  6. Division of Cardiology, University Children’s Hospital Zürich, Zürich, Switzerland

    Christian Balmer

  7. Christine Kühne-Center for Allergy Research and Education, Hochgebirgsklinik Davos, University Children’s Hospital Zürich, Zürich, Switzerland

    Roger Lauener

Authors
  1. Marianne Rohrbach
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  2. Andrea Klein
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  3. Alice Köhli-Wiesner
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  4. Dorothe Veraguth
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  5. Ianina Scheer
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  6. Christian Balmer
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  7. Roger Lauener
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  8. Matthias R. Baumgartner
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Corresponding author

Correspondence to Marianne Rohrbach.

Additional information

Communicated by: Frits Wijburg

Electronic database: MIM #232300

Competing interest: None declared.

Marianne Rohrbach and Andrea Klein contributed equally to this work

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Rohrbach, M., Klein, A., Köhli-Wiesner, A. et al. CRIM-negative infantile Pompe disease: 42-month treatment outcome. J Inherit Metab Dis 33, 751–757 (2010). https://doi.org/10.1007/s10545-010-9209-0

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  • DOI: https://doi.org/10.1007/s10545-010-9209-0

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