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Haematopoietic Stem Cell Transplantation Arrests the Progression of Neurodegenerative Disease in Late-Onset Tay-Sachs Disease

  • Research Report
  • Chapter
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JIMD Reports, Volume 41

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

Abstract

Tay-Sachs disease is a rare metabolic disease caused by a deficiency of hexosaminidase A that leads to accumulation of GM2 gangliosides predominantly in neural tissue. Late-onset Tay-Sachs disease variant is associated with a higher level of residual HexA activity. Treatment options are limited, and there are a few described cases who have undergone haematopoietic stem cell transplantation (HSCT) with variable outcome.

We describe a case of a 23-year-old male patient who presented with a long-standing tremor since 7 years of age. He had gait ataxia, a speech stammer and swallowing problems. His condition had had a static course apart from his tremor that had been gradually deteriorating. Because of the deterioration in his neurological function, the patient had an uneventful, matched-sibling donor bone marrow transplant at the age of 15 years. Eight years post-HSCT, at the age of 23, he retains full donor engraftment, and his white cell beta-HexA of 191 nmol/mg/h is comparable to normal controls (in-assay control = 187). He continues to experience some intentional tremor that is tolerable for daily life and nonprogressive since HSCT.

Conclusion: HSCT is a potential treatment option which might arrest neurodegeneration in patients with LOTS.

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Abbreviations

GA2:

GalNAc beta1-4 Gal beta 1-4 Glc-ceramide

GM2:

GalNAc beta 1-4 [NeuAc alpha 2-3] Gal beta 1-4 Glc-ceramide

Hexa A/B:

Hexosaminidase A/B

HSC:

Haematopoietic stem cell

HSCT:

Haematopoietic stem cell transplantation

Lc3:

GlcNAc beta1-3 Gal beta 1-4 Glc-ceramide

LOTS:

Late-onset Tay-Sachs

LSD:

Lysosomal storage disease

TSD:

Tay-Sachs disease

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Author information

Authors and Affiliations

  1. The Mark Holland Metabolic Unit, Adult Inherited Metabolic Disorders, Salford Royal NHS Foundation Trust, Salford, UK

    Karolina M. Stepien, Christian J. Hendriksz & Ana Jovanovic

  2. Department of Paediatric Blood and Marrow Transplant, Royal Manchester Children’s Hospital, Manchester, UK

    Su Han Lum & Robert Wynn

  3. Willink Biochemical Genetics Department, St. Mary’s Hospital, Manchester, UK

    J. Edmond Wraith, Heather J. Church & Simon Jones

  4. Department of Pharmacology, University of Oxford, Oxford, UK

    David Priestman & Frances M. Platt

  5. Steve Biko Academic Unit, Paediatrics and Child Health, University of Pretoria, Pretoria, South Africa

    Christian J. Hendriksz

Authors
  1. Karolina M. Stepien
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  2. Su Han Lum
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  3. J. Edmond Wraith
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  4. Christian J. Hendriksz
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  5. Heather J. Church
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  6. David Priestman
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  7. Frances M. Platt
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  8. Simon Jones
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  9. Ana Jovanovic
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  10. Robert Wynn
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Corresponding author

Correspondence to Karolina M. Stepien .

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: Gregory M. Pastores, MD

Appendices

Synopsis

HSCT is a potential disease modifying therapy for late-onset Tay-Sachs disease.

General Rules

Details of the Contributions of Individual Authors

KMS conception and design, analysis and interpretation of data, drafting the chapter and revising the chapter critically for important intellectual content.

SHM conception and design, analysis and interpretation of data, drafting the chapter and revising the chapter critically for important intellectual content.

JEW conception and design and analysis and interpretation of data.

CJH revising the chapter critically for important intellectual content.

HC acquisition of data and interpretation of data.

DP conception and design, analysis and interpretation of data, drafting the chapter and revising the chapter critically for important intellectual content.

FP revising the chapter critically for important intellectual content.

SJ acquisition of data and revising the chapter critically for important intellectual content.

AJ acquisition of data and revising the chapter critically for important intellectual content.

RW conception and design, analysis and interpretation of data, drafting the chapter and revising the chapter critically for important intellectual content.

All authors read and approved the manuscript before submission.

The Name of the Corresponding Author

Karolina M. Stepien.

The Mark Holland Metabolic Unit.

Adult Inherited Metabolic Disorders.

Salford, M6 8HD.

Tel 0161 2064365.

A Competing Interest Statement

KS received travel grants from Genzyme, Shire, BioMarin, Amicus and Alexion. She has conflict of interest for this publication.

SHL has no conflict of interest for this publication.

JEW has no conflict of interest for this publication.

CJH is a consultant for Actelion, BioMarin, Chiesi Inventiva, Sanofi, Genzyme and Shire and is owner director of FYMCA Medical Ltd.

HC has no conflict of interest for this publication.

DP has no conflict of interest for this publication.

FP is a co-founder of IntraBio and consultant to IntraBio, Actelion and Orphazyme. She has conflict of interest for this publication.

SJ has no conflict of interest for this publication.

AJ has no conflict of interest for this publication.

RW has no conflict of interest for this publication.

Details of funding: N/A.

Details of ethics approval: patient’s consent to bone marrow transplant includes consent to use of transplant outcome data.

A patient consent statement: patient’s consent was obtained.

Documentation of approval from the Institutional Committee for Care and Use of Laboratory Animals (or comparable committee): N/A.

Guarantor: RW.

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© 2017 Society for the Study of Inborn Errors of Metabolism (SSIEM)

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Stepien, K.M. et al. (2017). Haematopoietic Stem Cell Transplantation Arrests the Progression of Neurodegenerative Disease in Late-Onset Tay-Sachs Disease. 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_2017_76

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  • DOI: https://doi.org/10.1007/8904_2017_76

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  • Print ISBN: 978-3-662-58080-6

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