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

  • Karolina M. StepienEmail author
  • Su Han Lum
  • J. Edmond Wraith
  • Christian J. Hendriksz
  • Heather J. Church
  • David Priestman
  • Frances M. Platt
  • Simon Jones
  • Ana Jovanovic
  • Robert Wynn
Research Report
Part of the JIMD Reports book series (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.

Keywords

Haematopoietic stem cell transplantation Late onset Tay-Sachs disease 

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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Copyright information

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

Authors and Affiliations

  • Karolina M. Stepien
    • 1
    Email author
  • Su Han Lum
    • 2
  • J. Edmond Wraith
    • 3
  • Christian J. Hendriksz
    • 1
    • 5
  • Heather J. Church
    • 3
  • David Priestman
    • 4
  • Frances M. Platt
    • 4
  • Simon Jones
    • 3
  • Ana Jovanovic
    • 1
  • Robert Wynn
    • 2
  1. 1.The Mark Holland Metabolic Unit, Adult Inherited Metabolic DisordersSalford Royal NHS Foundation TrustSalfordUK
  2. 2.Department of Paediatric Blood and Marrow TransplantRoyal Manchester Children’s HospitalManchesterUK
  3. 3.Willink Biochemical Genetics DepartmentSt. Mary’s HospitalManchesterUK
  4. 4.Department of PharmacologyUniversity of OxfordOxfordUK
  5. 5.Steve Biko Academic Unit, Paediatrics and Child HealthUniversity of PretoriaPretoriaSouth Africa

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