Publication: A convenient approach to facilitate monitoring Gaucher disease progression and therapeutic response
Issued Date
2017-09-21
Resource Type
ISSN
13645528
00032654
00032654
Other identifier(s)
2-s2.0-85029157639
Rights
Mahidol University
Rights Holder(s)
SCOPUS
Bibliographic Citation
Analyst. Vol.142, No.18 (2017), 3380-3387
Suggested Citation
Wujuan Zhang, Melissa Oehrle, Carlos E. Prada, Ida Vanessa D. Schwartz, Somchai Chutipongtanate, Duangrurdee Wattanasirichaigoon, Venette Inskeep, Mei Dai, Dao Pan, Ying Sun, Kenneth D.R. Setchell A convenient approach to facilitate monitoring Gaucher disease progression and therapeutic response. Analyst. Vol.142, No.18 (2017), 3380-3387. doi:10.1039/c7an00938k Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/41803
Research Projects
Organizational Units
Authors
Journal Issue
Thesis
Title
A convenient approach to facilitate monitoring Gaucher disease progression and therapeutic response
Abstract
© 2017 The Royal Society of Chemistry. Gaucher disease (GD) is caused by mutations on the GBA1 gene leading to deficiency in acid β-glucosidase (GCase) and subsequent accumulation of its substrates, glucosylceramide (GlcC) and glucosylsphingosine (GlcS). GlcS in plasma has been proposed as a highly sensitive and specific biomarker for the diagnosis of GD and for monitoring disease progression and response to therapy. Here we report a novel robust and accurate hydrophilic interaction liquid chromatography tandem mass spectrometric method (HILIC-MS/MS) for the direct measurement of glucosylsphingosine (GlcS) in dried plasma spots (DPS). The method was also capable of resolving the isomeric pair, glucosylsphingosine and galactosylsphingosine, the latter of which was proposed as a promising biomarker for Krabbe disease. The method was fully validated and applied to the analysis of 19 GD patients and carriers. The GlcS levels in 9 GD type I patients who have been on enzyme replacement therapy (ERT) were reduced to a mean of 31.0 nM, much lower compared to a pre-treated specimen at a level of 85.8 nM, but still significantly elevated compared to healthy controls. GlcS concentrations in three treated type III GD patients were much lower compared to an untreated patient. In our preclinical GD studies, 4L;C∗ mice (subacute nGD model) exhibited comparable levels of plasma GlcS, but had much higher GlcS accumulation in the brain than those of 9V/null mice (chronic neuropathic GD model). Our method for the measurement of GlcS in DPS proved to be a very convenient approach for sample collection, storage and shipping nationwide and internationally.