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Effectiveness of Early Hematopoietic Stem Cell Transplantation in Preventing Neurocognitive Decline in Mucopolysaccharidosis Type II: A Case Series

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JIMD Reports, Volume 41

Part of the book series: JIMD Reports ((JIMD,volume 41))

Abstract

The early progressive form of the X-linked disorder, Hunter syndrome or mucopolysaccharidosis type II (MPS II) (OMIM #309900), is characterized by cognitive decline, and pulmonary and cardiac complications that often cause death before 20 years of age. Deficiency of the lysosomal enzyme, iduronate-2-sulfatase (EC 3.1.6.13) results in deposition of the glycosaminoglycans, dermatan, and heparan sulfate in various tissues. In recent years, enzyme replacement therapy (ERT) has become the mainstay of treatment, but is expensive and ineffective in arresting cognitive decline. Hematopoietic stem cell transplantation (HSCT) also provides enzyme replacement, and may be effective in stabilizing neurocognitive function if initiated early, though data are limited. We present a case series of four patients who demonstrated neurocognitive stabilization with early HSCT. HSCT is a potentially underutilized treatment strategy for select groups of MPS II patients.

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Abbreviations

ADL:

Activities of daily living

ATG:

Anti-thymocyte globulin

AUC:

Area Under Curve

CNS:

Central nervous system

CSF:

Cerebrospinal fluid

CT:

Computed tomography

DAS-II:

Differential Ability Scales, Second Edition

DQ:

Developmental quotient

ERT:

Enzyme replacement therapy

HLA:

Human leukocyte antigen

HSCT:

Hematopoietic stem cell transplantation

IDS:

Iduronate-2-sulfatase

IQ:

Intelligence quotient

MPS:

Mucopolysaccharidosis

MPS I:

Mucopolysaccharidosis type I (Hurler syndrome)

MPS II:

Mucopolysaccharidosis type II (Hunter syndrome)

MRI:

Magnetic resonance imaging

WISC-IV:

Weschler Intelligence Scale for Children 4th Edition

WPPSI III:

Weschler Preschool and Primary Intelligence Scale 3rd Edition

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Author information

Authors and Affiliations

  1. Genetic Metabolic Disorders Service, The Children’s Hospital at Westmead, Westmead, NSW, Australia

    A. Selvanathan, C. Ellaway, P. Owens & K. Bhattacharya

  2. Discipline of Child and Adolescent Health, The University of Sydney, Camperdown, NSW, Australia

    A. Selvanathan, C. Ellaway, P. J. Shaw & K. Bhattacharya

  3. Starship Paediatric Metabolic Service, Starship Children’s Hospital, Auckland, New Zealand

    C. Wilson

  4. Blood and Marrow Transplant Service, The Children’s Hospital at Westmead, Westmead, NSW, Australia

    P. J. Shaw

Authors
  1. A. Selvanathan
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  2. C. Ellaway
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  3. C. Wilson
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  4. P. Owens
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  5. P. J. Shaw
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  6. K. Bhattacharya
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Corresponding author

Correspondence to A. Selvanathan .

Editor information

Editors and Affiliations

  1. Tulane University Medical School, New Orleans, LA, USA

    Eva Morava

  2. Division of Metabolism & Children’s Research Centre, University Children’s Hospital Zürich, Zürich, Switzerland

    Matthias Baumgartner

  3. Division of Child and Adolescent Neurology, Mayo Clinic, Rochester, MN, USA

    Marc Patterson

  4. Clinical and Molecular Genetics Unit, UCL Institute of Child Health, London, UK

    Shamima Rahman

  5. Division of Human Genetics, Medical University Innsbruck, Innsbruck, Austria

    Johannes Zschocke

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

    Verena Peters

Additional information

Communicated by: Verena Peters

Appendices

Synopsis

Hematopoietic stem cell transplantation is an under-recognized but effective therapy that stabilizes neurocognitive function in patients with mucopolysaccharidosis type II.

Contributions of Authors

Arthavan Selvanathan: planning of project, retrieving and analyzing files, performing literature review, creating initial draft of the chapter, editing the chapter, submission process, correspondence with journal.

Carolyn Ellaway: planning of project, submission of ethics approval, clinical management of patients, analyzing files, editing the chapter.

Callum Wilson: clinical management of patients, analyzing medical records, editing the chapter.

Penny Owens: clinical management of patients, editing the chapter.

Peter Shaw: planning of project, clinical management of patients, analyzing files, editing the chapter.

Kaustuv Bhattacharya: planning of project, clinical management of patients, analyzing files, editing the chapter.

Compliance with Ethics Guidelines

Ethics approval was granted by the Sydney Children’s Hospital Network Research Ethics and Governance Team (HREC Reference Number: CCR2016/09). All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000. Informed consent was obtained from all patients’ families in order to review medical records, and publish their cases anonymized.

Correspondence and Statement of Competing Interests

I, Arthavan Selvanathan, serve as corresponding author and guarantor for this chapter. None of the authors have received or accepted reimbursements or funding in relation to the material in this chapter.

All authors (Arthavan Selvanathan, Carolyn Ellaway, Callum Wilson, Penny Owens, Peter Shaw and Kaustuv Bhattacharya) declare they have no conflicts of interest.

Competing Interests: None declared.

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© 2018 Society for the Study of Inborn Errors of Metabolism (SSIEM)

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Selvanathan, A., Ellaway, C., Wilson, C., Owens, P., Shaw, P.J., Bhattacharya, K. (2018). Effectiveness of Early Hematopoietic Stem Cell Transplantation in Preventing Neurocognitive Decline in Mucopolysaccharidosis Type II: A Case Series. In: Morava, E., Baumgartner, M., Patterson, M., Rahman, S., Zschocke, J., Peters, V. (eds) JIMD Reports, Volume 41. JIMD Reports, vol 41. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2018_104

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  • DOI: https://doi.org/10.1007/8904_2018_104

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  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-662-58080-6

  • Online ISBN: 978-3-662-58081-3

  • eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)

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