Groener J E M, Poorthuis B J H M, Kuiper S, Hollak C E M, Aerts J M F G
Department of Medical Biochemistry, University of Amsterdam, Academic Medical Center, Amsterdam, the Netherlands.
Biochim Biophys Acta. 2008 Jan-Feb;1781(1-2):72-8. doi: 10.1016/j.bbalip.2007.11.004. Epub 2007 Dec 5.
The concentrations of plasma glucosylceramide (GlcCer) and ceramide (Cer) were determined in a cohort of type 1 Gaucher disease patients. In plasma of untreated patients, GlcCer concentrations were on average 3-fold increased (median Gaucher: 17.5 nmol/ml, range: 6.5-45.5 (n=27); median control: 5.9 nmol/ml, range 4.0-8.6 (n=15)). Although plasma Cer concentrations were not significantly different between the two groups (median Gaucher: 7.2 nmol/ml, range: 4.2-10.9 (n=27); median control: 7.8 nmol/ml, range 5.7-11.9 (n=15)) in individual patients plasma GlcCer/Cer ratio yields slightly better discrimination between Gaucher disease patients and normal individuals than the GlcCer levels. Positive correlations were detected between plasma GlcCer concentration and GlcCer/Cer ratio and severity of disease, plasma chitotriosidase and CCL18, surrogate markers of storage cells. Gaucher disease is treated by enzyme replacement and substrate reduction therapy. Both therapies were found to result in decreases in plasma GlcCer already within 6 months, without causing abnormal plasma GlcCer or Cer concentrations. The corrections in plasma GlcCer were most robust in patients with a pronounced clinical response. In conclusion, plasma GlcCer concentration and GlcCer/Cer ratio is of value to monitor Gaucher disease manifestation and response to therapeutic intervention.
在一组1型戈谢病患者中测定了血浆葡萄糖神经酰胺（GlcCer）和神经酰胺（Cer）的浓度。在未经治疗的患者血浆中，GlcCer浓度平均升高了3倍（戈谢病患者中位数：17.5 nmol/ml，范围：6.5 - 45.5（n = 27）；对照中位数：5.9 nmol/ml，范围4.0 - 8.6（n = 15））。尽管两组之间血浆Cer浓度无显著差异（戈谢病患者中位数：7.2 nmol/ml，范围：4.2 - 10.9（n = 27）；对照中位数：7.8 nmol/ml，范围5.7 - 11.9（n = 15）），但在个体患者中，血浆GlcCer/Cer比值在区分戈谢病患者和正常个体方面比GlcCer水平稍好。血浆GlcCer浓度与GlcCer/Cer比值以及疾病严重程度、血浆壳三糖苷酶和CCL18（储存细胞的替代标志物）之间存在正相关。戈谢病通过酶替代疗法和底物减少疗法进行治疗。发现这两种疗法在6个月内均导致血浆GlcCer降低，且未引起血浆GlcCer或Cer浓度异常。血浆GlcCer的校正值在有明显临床反应的患者中最为显著。总之，血浆GlcCer浓度和GlcCer/Cer比值对于监测戈谢病的表现和对治疗干预的反应具有重要价值。
