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.
Competing interests: None declared
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Communicated by: Maurizio Scarpa, M.D, Ph.D
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Lindsey Welling, Jaap Jan Boelens, Jan Pieter Marchal, Peter van Hasselt Ans T. van der Ploeg, and Frits A. Wijburg declare that they have no conflict of interest.
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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 (5). Informed consent was obtained from the parents of the patients included in the study. Additional informed consent was obtained for all patients for which identifying information is included in this article.
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Lindsey Welling: reporting
Jaap Jan Boelens: treating physician, coordinating the performed examinations
Jan Pieter Marchal: interpreting neuropsychological test results, reporting
Peter van Hasselt: treating physician, reporting
Ans T. van der Ploeg: reporting
Frits A. Wijburg: reporting
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Welling, L., Marchal, J.P., van Hasselt, P., van der Ploeg, A.T., Wijburg, F.A., Boelens, J.J. (2014). Early Umbilical Cord Blood-Derived Stem Cell Transplantation Does Not Prevent Neurological Deterioration in Mucopolysaccharidosis Type III. In: Zschocke, J., Baumgartner, M., Morava, E., Patterson, M., Rahman, S., Peters, V. (eds) JIMD Reports, Volume 18. JIMD Reports, vol 18. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2014_350
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DOI: https://doi.org/10.1007/8904_2014_350
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