Dried blood spot analysis: an easy and reliable tool to monitor the biochemical effect of hematopoietic stem cell transplantation in hurler syndrome patients

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 (r(2) = .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.