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Early Umbilical Cord Blood-Derived Stem Cell Transplantation Does Not Prevent Neurological Deterioration in Mucopolysaccharidosis Type III

  • Lindsey Welling
  • Jan Pieter Marchal
  • Peter van Hasselt
  • Ans T. van der Ploeg
  • Frits A. WijburgEmail author
  • Jaap Jan Boelens
Case Report
Part of the JIMD Reports book series (JIMD, volume 18)

Abstract

Mucopolysaccharidosis type III (MPS III), or Sanfilippo disease, is a neurodegenerative lysosomal storage disease (LSD) caused by defective lysosomal degradation of heparan sulfate (HS). No effective disease-modifying therapy is yet available. In contrast to some other neuronopathic LSDs, bone marrow-derived hematopoietic stem cell transplantation (HSCT) fails to prevent neurological deterioration in MPS III patients. We report on the 5-year outcome of early transplantation, i.e., before onset of clinical neurological disease, in combination with the use of umbilical cord blood-derived hematopoietic stem cells (UCBT), in two MPS III patients. Both patients had a normal developmental quotient at the time of UCBT. One patient had a combination of mutations predicting a classical severe phenotype (MPS IIIA), and one patient (MPS IIIB) had mutations predicting a very attenuated phenotype. Transplantation was uncomplicated with full engraftment of donor cells in both.

Both patients showed progressive neurological deterioration with regression of cognitive skills and behavioral disturbances during 5 years after successful UCBT, comparable to the natural history of patients with the same combination of mutations. The concentration of HS in CSF in the patient with the attenuated phenotype of MPS IIIB 2 years after UCBT was very high and in the range of untreated MPS III patients.

We conclude that the course of cognitive development, behavioral problems, and absence of biochemical correction in CSF demonstrate the absence of relevant effect of UCBT in MPS III patients, even when performed before clinical onset of CNS disease.

Keywords

Hematopoietic Stem Cell Transplantation Central Nervous System Disease Lysosomal Storage Disease Developmental Quotient Umbilical Cord Blood Transplantation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© SSIEM and Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Lindsey Welling
    • 1
  • Jan Pieter Marchal
    • 2
  • Peter van Hasselt
    • 3
  • Ans T. van der Ploeg
    • 4
  • Frits A. Wijburg
    • 1
    Email author
  • Jaap Jan Boelens
    • 5
  1. 1.Division of Metabolic Diseases (H7-270), Department of Pediatrics and Amsterdam Lysosome Center “Sphinx”Academic Medical Center (AMC), University of AmsterdamAmsterdamThe Netherlands
  2. 2.Psychosocial DepartmentAcademic Medical Center, University of AmsterdamAmsterdamThe Netherlands
  3. 3.Department of Pediatric Gastroenterology and Metabolic DiseasesWilhelmina Children’s Hospital, University Medical Center UtrechtUtrechtThe Netherlands
  4. 4.Department of Pediatrics and Center for Lysosomal and Metabolic DiseasesErasmus MC University Medical CenterRotterdamThe Netherlands
  5. 5.Pediatric Blood and Marrow Transplantation ProgramWilhelmina Children’s Hospital, University Medical Center UtrechtUtrechtThe Netherlands

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