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Value of plasma chitotriosidase to assess non-neuronopathic Gaucher disease severity and progression in the era of enzyme replacement therapy

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Journal of Inherited Metabolic Disease

Abstract

Gaucher disease (GD) is caused by deficiency of the enzyme glucocerebrosidase catalysing the regular lysosomal degradation of glucosylceramide. In the common non-neuropathic variant of GD, glucosylceramide-laden macrophages (Gaucher cells) accumulate in various tissues. Gaucher cells secrete chitotriosidase, an active chitinase, resulting in increased plasma chitotriosidase levels, which can be sensitively monitored by an enzyme activity assay. Plasma chitotriosidase is a rough estimate of body burden of Gaucher cells. Non-neuronopathic GD is presently treated by enzyme replacement therapy (ERT) and substrate reduction therapy (SRT). We addressed the question whether plasma chitotriosidase acts as (predictive) marker of clinical manifestations in non-neuronopathic GD patients receiving treatment. Reductions in plasma chitotriosidase during therapy correlated with corrections in liver and spleen volumes and showed positive trends with improvements in haemoglobin and platelet count and bone marrow composition. The occurrence of long-term complications and associated conditions such as multiple myeloma, bone complications, Parkinson’s disease, hepatocellular carcinoma and pulmonary hypertension positively correlated with the plasma chitotriosidase level pre-therapy, the average plasma chitotriosidase during 3 years of ERT and the residual plasma chitotriosidase after 2 years of ERT. In summary, plasma chitotriosidase is a valuable marker in the assessment and follow-up of GD patients.

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Acknowledgments

The authors would like to acknowledge Wilma Donker-Koopman, Karen Ghauharali-van der Vlugt, Saskia Scheij, Marri Verhoek, Sonja van Weely and Maaike Wiersma who are responsible for the chitotriosidase measurements, results and/or collecting patient samples.

Conflict of Interest

Laura van Dussen has received travel reimbursements at two occasions (Genzyme, Protalix).

Erik Hendriks, Ans (JEM) Groener, Rolf Boot and Hans (JMFG) Aerts have nothing to disclose.

Carla EM Hollak received reimbursements of travel costs and honoraria for participation in symposia and speakers bureaus from Actelion, Protalix, Genzyme and Shire. All honoraria are donated to research funds at the AMC.

Animal Rights

This article does not contain any studies with animal subjects performed by the any of the authors.

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Authors and Affiliations

  1. Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, PO box 22660, 1100 DD, Amsterdam, The Netherlands

    L. van Dussen & C. E. M. Hollak

  2. Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

    E. J. Hendriks, J. E. M. Groener, R. G. Boot & J. M. F. G. Aerts

Authors
  1. L. van Dussen
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  2. E. J. Hendriks
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  3. J. E. M. Groener
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  4. R. G. Boot
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  5. C. E. M. Hollak
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  6. J. M. F. G. Aerts
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Correspondence to L. van Dussen.

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Communicated by: Maurizio Scarpa

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van Dussen, L., Hendriks, E.J., Groener, J.E.M. et al. Value of plasma chitotriosidase to assess non-neuronopathic Gaucher disease severity and progression in the era of enzyme replacement therapy. J Inherit Metab Dis 37, 991–1001 (2014). https://doi.org/10.1007/s10545-014-9711-x

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  • DOI: https://doi.org/10.1007/s10545-014-9711-x

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