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Comparison of recent pivotal recommendations for the diagnosis and treatment of late-onset Pompe disease using diagnostic nodes—the Pompe disease burden scale

Journal of Neurology volume 266, pages 2010–2017 (2019)Cite this article

Abstract

Pompe disease is a rare autosomal-recessive disorder characterised by limb-girdle myopathy and respiratory weakness in the late-onset form (LOPD). Various mutations in the acid alpha-glucosidase gene lead to toxic lysosomal and extra-lysosomal glycogen accumulation in all organs due to ineffective glycogen clearance by the encoded enzyme. Only one randomized trial demonstrated beneficial effects of respiratory function and meters walked in the 6-min walking test with enzyme replacement therapy (ERT). These results were confirmed in several retrospective and prospective observations and in meta-analyses. Due to a potential lifelong therapy, moderate efficacy and high treatment costs time of ERT initiation and cessation is an ongoing matter of debate. So far, several national and international recommendations have been published with different criteria concerning diagnosis, initiation and cessation of ERT in LOPD. We therefore formally analysed recent published recommendations and consensus statements of LOPD using diagnostic nodes (DODES) as a special software tool. With DODES, an objective analysis becomes possible if the content of the recommendations is represented as algorithms using cross-compatible elements. This analysis formally disclosed both, areas of great heterogeneity and concordance for the diagnosis and management of LOPD and paved the way for a Pompe disease burden scale focussing on ERT initiation. According to this investigation further clinical research should concentrate on ERT in pre-symptomatic and severely affected LOPD patients and on cessation criteria for ERT as these issues are areas of international uncertainty and discordance.

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Author information

Author notes

  1. Kai Michael Rösler

    Present address: Neurozentrum Basel, Marktplatz 5, 4001, Basel, Switzerland

Affiliations

  1. Department of Neurology, Cantonal Hospital St. Gallen, Rorschacherstrasse 95, 9007, St. Gallen, Switzerland

    Thomas Hundsberger & Daniela Leupold

  2. Department of Neurology, Friedrich-Baur-Institute, Ludwig-Maximilians-University, 80336, Munich, Germany

    Benedikt Schoser

  3. Department of Neurology, Royal Melbourne Hospital, Grattan street, Parkville, Victoria, 3052, Australia

    Daniela Leupold

  4. Department of Neurology, University of Bern, Inselspital, 3010, Bern, Switzerland

    Kai Michael Rösler

  5. Department of Radiation Oncology, Cantonal Hospital, 9007, St. Gallen, Switzerland

    Paul Martin Putora

  6. Department of Radiation Oncology, University of Bern, Inselspital, 3010, Bern, Switzerland

    Paul Martin Putora

Authors
  1. Thomas Hundsberger
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  2. Benedikt Schoser
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  3. Daniela Leupold
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  4. Kai Michael Rösler
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Corresponding author

Correspondence to Thomas Hundsberger.

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Conflicts of interest

TH served as a scientific advisor for and received institutional grants from Sanofi Genzyme (Switzerland). BS is a scientific advisor of Audentes Therapeutics. Lupin Therapeutics and Nexien BioPharma, Inc. He received speaker honoraria from Sanofi Genzyme, Amicus therapeutics, and Kedrion. He received unrestricted research grants from Sanofi Genzyme and Grennovation. KMR was a scientific advisor for Sanofi Genzyme (Switzerland) and Biogen Switzerland AG; and has received speaker honoraria from Sanofi Genzyme (Switzerland) and Shire Switzerland GmbH. DL declares no conflict of interest. PMP received institutional research or educational grants from AstraZeneca, Celgene, Sanofi Genzyme and Roche.

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The manuscript does not contain clinical studies or patient data and was done as a literature analysis. Therefore, no formal IRB approval was submitted.

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Hundsberger, T., Schoser, B., Leupold, D. et al. Comparison of recent pivotal recommendations for the diagnosis and treatment of late-onset Pompe disease using diagnostic nodes—the Pompe disease burden scale. J Neurol 266, 2010–2017 (2019). https://doi.org/10.1007/s00415-019-09373-2

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  • DOI: https://doi.org/10.1007/s00415-019-09373-2

Keywords

  • Pompe disease
  • Enzyme replacement therapy
  • ERT initiation
  • ERT cessation
  • Diagnostic nodes
  • Guidelines