Dried Blood Spot Analysis: An Easy and Reliable Tool to Monitor the Biochemical Effect of Hematopoietic Stem Cell Transplantation in Hurler Syndrome Patients

Research output: Contribution to journalArticle

Abstract

Hurler syndrome (HS), the most severe phenotype in the spectrum of mucopolysaccharidosis type I, is caused by a deficiency of the lysosomal enzyme alpha-L-iduronidase (IDUA). At present, hematopoietic stem cell transplantation (HSCT) is the only treatment able to prevent disease progression in the central nervous system, and therefore considered the treatment of choice in HS patients. Because IDUA enzyme activities after HSCT have been suggested to influence the prognosis of HS patients, monitoring these activities after HSCT remains highly important. The use of dried blood spots (DBS) for enzyme analysis can be a useful alternative to the conventional leukocyte assay. Importantly, this method allows for convenient worldwide shipment, and can therefore be applied to monitor patients from larger areas of the world, or during large-scale international studies. Furthermore, this method requires only a minimal amount of blood. From 13 HS patients receiving HSCT, 36 paired whole blood and DBS samples were analyzed to assess leukocyte and DBS IDUA activities, respectively. To correct for potential interfering factors, simultaneous assay of the alpha-Galactosidase-A (AGA) activity was performed in the DBS samples and an IDUA/AGA ratio was calculated. A strong linear correlation was demonstrated between the DBS IDUA/AGA ratio and the leukocyte IDUA activity (r2 = .875, P < .001). This correlation was applicable to all enzyme activities, including the activities measured early after HSCT as well as heterozygous activities because of mixed chimerism or the use of a carrier donor. These results demonstrate that the DBS method is reliable to monitor the biochemical effect of HSCT in HS patients.

Details

Authors
  • Mieke Aldenhoven
  • Tom J. de Koning
  • Frans W. Verheijen
  • Berthil H. Prinsen
  • Frits A. Wijburg
  • Ans T. van der Ploeg
  • Monique G.M. de Sain-van der Velden
  • Jaap Jan Boelens
External organisations
  • University Medical Center Utrecht
  • Erasmus University Rotterdam
  • Academic Medical Center of University of Amsterdam (AMC)
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Biochemistry and Molecular Biology
  • Medical and Health Sciences

Keywords

  • Clinical enzyme tests, Dried blood spot, Hematopoietic stem cell transplantation, Hurler syndrome, Iduronidase, Mucopolysaccharidosis I
Original languageEnglish
Pages (from-to)701-704
Number of pages4
JournalBiology of Blood and Marrow Transplantation
Volume16
Issue number5
Publication statusPublished - 2010 May 1
Publication categoryResearch
Peer-reviewedYes
Externally publishedYes