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. Wijburg*, Jaap Jan Boelens

*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceedingChapterAcademicpeer-review

13 Citations (Scopus)
1 Downloads (Pure)

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.

Original languageEnglish
Title of host publicationJIMD Reports
PublisherSpringer
Pages63-68
Number of pages6
Volume18
DOIs
Publication statusPublished - 1 Jan 2015

Publication series

NameJIMD Reports
Volume18
ISSN (Print)2192-8304
ISSN (Electronic)2192-8312

Keywords

  • Central nervous system disease
  • Developmental quotient
  • Hematopoietic stem cell transplantation
  • Lysosomal storage disease
  • Umbilical cord blood transplantation

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