Department of Hematology, Immunology and Stem Cell Transplantation University Medical Center, Utrecht, The Netherlands.
Biol Blood Marrow Transplant. 2010 May;16(5):701-4. doi: 10.1016/j.bbmt.2010.01.006. Epub 2010 Jan 21.
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.
黏多糖贮积症 I 型（MPS I）是一种溶酶体贮积症，Hurler 综合征（HS）是其最严重的表型，由溶酶体酶α-L-艾杜糖苷酸酶（IDUA）缺乏引起。目前，造血干细胞移植（HSCT）是唯一能够预防中枢神经系统疾病进展的治疗方法，因此被认为是 HS 患者的首选治疗方法。由于 IDUA 酶活性在 HSCT 后被认为会影响 HS 患者的预后，因此 HSCT 后监测这些酶活性仍然非常重要。使用干血斑（DBS）进行酶分析可以作为传统白细胞检测的有用替代方法。重要的是，这种方法允许方便地在全球范围内运输，因此可以应用于监测来自世界更大地区的患者，或在大型国际研究中应用。此外，这种方法只需要少量的血液。从 13 名接受 HSCT 的 HS 患者中，分析了 36 对全血和 DBS 样本，以分别评估白细胞和 DBS IDUA 活性。为了校正潜在的干扰因素，同时在 DBS 样本中测定α-半乳糖苷酶-A（AGA）活性，并计算 IDUA/AGA 比值。DBS IDUA/AGA 比值与白细胞 IDUA 活性之间显示出很强的线性相关性（r² =.875，P <.001）。这种相关性适用于所有酶活性，包括 HSCT 后早期测量的活性以及由于混合嵌合体或使用载体供体而导致的杂合活性。这些结果表明，DBS 方法可靠，可用于监测 HS 患者 HSCT 的生化效应。
