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Prevalence and Development of Orthopaedic Symptoms in the Dutch Hurler Patient Population after Haematopoietic Stem Cell Transplantation

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Book cover JIMD Reports – Case and Research Reports, 2012/6

Part of the book series: JIMD Reports ((JIMD,volume 9))

Abstract

Hurler syndrome (MPS-IH) is a rare autosomal recessive lysosomal storage disease. Besides a variety of other features, Hurler syndrome is characterized by a range of skeletal abnormalities known as dysostosis multiplex. Despite the successful effect of haematopoietic stem cell transplantation on the other features, dysostosis remains a disabling symptom of the disease. This study analyzed the status and development of the orthopaedic manifestations of 14 Dutch Hurler patients after stem cell transplantation.

Data were obtained retrospectively by reviewing patients’ charts, radiographs and MRIs. Existing methods to measure the deficiencies were modified to optimally address the dysostosis. These measurements were done by two of the authors independently. The odontoïd/body ratio, kyphotic angle, scoliotic angle and parameters for hip dysplasia and genu valgum were measured and plotted against age. The degree of progression was determined. The intraclass correlation coefficient (ICC) was calculated to determine the reliability of the measurements.

All patients showed hypoplasia of the odontoïd, which significantly improved during growth. Kyphosis in the thoracolumbar area was present in 13 patients and proved to be progressive. Scoliosis was observed in eight patients. Hip dysplasia was present in all patients and showed no tendency of improvement. In all but one patient, knee valgus remained more than two standard deviations above normal.

Dysostosis remains a major problem after haematopoietic stem cell transplantation in Hurler patients. Moreover, except for dens hypoplasia, it appears to be progressive and therefore surgical interventions may be necessary in the majority of these patients.

Competing interests: None declared

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Acknowledgements

We would like to thank assistant professor R.K. Stellato, Department of Biostatistics, Julius Center, UMC Utrecht, for her help with the statistical design and analysis of our data.

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Authors and Affiliations

  1. Department of Orthopaedics, University Medical Center Utrecht, HP G 05.228, 85500, 3508 GA, Utrecht, The Netherlands

    F. J. Stoop, M. C. Kruyt, M. H. van der Linden, R. J. B. Sakkers & R. M. C. Castelein

  2. Department of Metabolic Diseases, Wilhelmina Children’s Hospital, University Medical Center, Utrecht, The Netherlands

    P. M. van Hasselt

Authors
  1. F. J. Stoop
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  2. M. C. Kruyt
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  3. M. H. van der Linden
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  4. R. J. B. Sakkers
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  5. P. M. van Hasselt
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  6. R. M. C. Castelein
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Corresponding author

Correspondence to M. C. Kruyt .

Editor information

Editors and Affiliations

  1. Sektionen für Humangenetik und Klinische, Medizinische Universität Innsbruck, Innsbruck, Austria

    Johannes Zschocke (Editors-in-Chief) (Editors-in-Chief)

  2. Biological Sciences, Michigan Technological University, Houghton, Michigan, USA

    K. Michael Gibson (Editors-in-Chief) (Editors-in-Chief)

  3. Department of Biochemistry Genetics Unit, University of Oxford, Oxford, UK

    Garry Brown (Editors) (Editors)

  4. Medical Center Department of Pediatrics IGMD, Radboud University Nijmegen, Nijmegen, Netherlands

    Eva Morava (Editors) (Editors)

  5. Center for Child and Adolescent Medicine, Heidelberg University Hospital, Heidelberg, Germany

    Verena Peters (Managing Editor) (Managing Editor)

Additional information

Communicated by: Robin Lachmann

Appendices

Take-Home Message

Dysostosis multiplex remains a major problem in Hurler patients after haematopoietic stem cell transplantation. Except for dens hypoplasia, it appears progressive and often requires surgical intervention.

Contribution of Individual Authors

The authors FS, MK and RS measured the degree of odontoïd dysplasia, kyphosis and malformation of the pelvis. The degree of scoliosis and genu valgum was measured by FS. Authors FS, MK and MV pooled and analyzed the data, and constructed the tables, figures and the first draft of the article. Authors FS, MK, MV, RS, PV and RC were involved in the set-up of the study, and in critically reviewing and editing the various drafts of the manuscript.

Guarantor of the Article

Dr. M.C. Kruyt

Competing Interests Statement

None of the authors have competing interests, based on the ‘Competing Interests Questions’.

Details of Funding

The authors confirm independence of sponsors.

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© 2012 SSIEM and Springer-Verlag Berlin Heidelberg

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Stoop, F.J., Kruyt, M.C., van der Linden, M.H., Sakkers, R.J.B., van Hasselt, P.M., Castelein, R.M.C. (2012). Prevalence and Development of Orthopaedic Symptoms in the Dutch Hurler Patient Population after Haematopoietic Stem Cell Transplantation. In: Zschocke, J., Gibson, K.M., Brown, G., Morava, E., Peters, V. (eds) JIMD Reports – Case and Research Reports, 2012/6. JIMD Reports, vol 9. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2012_175

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  • DOI: https://doi.org/10.1007/8904_2012_175

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  • Print ISBN: 978-3-642-35517-2

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