Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002986 (Fabry)
 5,646 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report a comparative study of triplex tandem mass spectrometry (MS/MS) based assays of lysosomal enzymes in dried blood spots for the early detection of Pompe, Fabry, and Hurler diseases in newborns. Four methods have been evaluated that differed in sample handling and the equipment used. A newly developed method uses assay quenching with acetonitrile to precipitate blood proteins followed by analysis on an LC-electrospray/MS/MS system capable of multiple consecutive sample injections on two parallel chromatographic columns. This method requires 1.5 min per a triplex analysis of enzyme products and internal standards, which matches the throughput of the previously reported flow injection method. LC separation reduces matrix effects and allows for more facile sample workup. The new LC-based method showed figures of merit that were superior to those of the currently used method based on liquid-liquid extraction into ethyl acetate and flow injection into the mass spectrometer. The other methods we investigated for comprehensive comparison involved liquid-liquid extraction into ethyl acetate followed by LC-ESI-MS/MS and acetonitrile quenching followed by direct flow injection. Both methods using acetonitrile quenching were found to be robust and provide good quality data while requiring fewer liquid transfer steps and less disposable material and labor than did the extraction methods. The individual merits of the new methods are discussed to present an evaluated alternative approach to high-throughput analysis in newborn screening laboratories.
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PMID:Comparative triplex tandem mass spectrometry assays of lysosomal enzyme activities in dried blood spots using fast liquid chromatography: application to newborn screening of Pompe, Fabry, and Hurler diseases. 2154 11

Background Lysosphingolipids, the N-deacylated forms of sphingolipids, have been identified as potential biomarkers of several sphingolipidoses, such as Gaucher, Fabry, Krabbe and Niemann-Pick diseases and in GM1 and GM2 gangliosidoses. To date, different methods have been developed to measure various lysosphingolipids (LysoSLs) in plasma. Here, we present a novel liquid chromatography tandem mass spectrometry (LC-MS/MS) assay for a simultaneous quantification of LysoSLs (HexSph, LysoGb3, LysoGM1, LysoGM2, LysoSM and LysoSM509) in dried blood spot (DBS). This LC-MS/MS method was used to compare the levels of LysoSLs in DBS and plasma in both affected patients and healthy controls. Methods Lysosphingolipids were extracted from a 3.2 mm diameter DBS with a mixture of methanol:acetonitrile:water (80:15:5, v/v) containing internal stable isotope standards. Chromatographic separation was performed using a C18 column with a gradient of water and acetonitrile both with 0.1% formic acid in a total run time of 4 min. The compounds were detected in the positive ion mode electrospray ionization (ESI)-MS/MS by multiple reaction monitoring (MRM). Results The method was validated on DBS to demonstrate specificity, linearity, lowest limit of quantification, accuracy and precision. The reference ranges were determined in pediatric and adult populations. The elevated levels of LysoSLs were identified in Gaucher disease (HexSph), Fabry disease (LysoGb3), prosaposin deficiency (HexSph and LysoGb3) and Niemann-Pick disease types A/B and C (LysoSM and LysoSM509). The correlation in the levels between DBS and plasma was excellent for LysoGb3 and HexSph but poor for LysoSM and LysoSM509. Conclusions Despite the fact that plasma LysoSLs determination remains the gold standard, our LC-MS/MS method allows a rapid and reliable quantification of lysosphingolipids in DBS. The method is a useful tool for the diagnosis of different sphingolipidoses except for Niemann-Pick type C.
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PMID:Plasma and dried blood spot lysosphingolipids for the diagnosis of different sphingolipidoses: a comparative study. 3166 16

Infrared attenuated total reflection (ATR) spectroscopy is a common laboratory technique for the analysis of highly absorbing liquids and solids. However, in a process environment, maintaining a sufficient sample exchange and cleaning of the sensitive surface of the element is a crucial issue. An important industrial application is the measurement of isocyanate concentrations. Isocyanates are necessary for the fabrication of polyurethane materials and are among the chemicals with the highest production volume worldwide. For process applications, narrowband photometers or MEMS spectrometers are more appropriate than the use of bulky FTIR instruments frequently encountered in a laboratory environment. Toluene diisocyanate (TDI) and hexamethylene diisocyanate (HDI) concentrations are measured with a planar ATR photometer setup. Using a miniature Fabry-Perot interferometer (FPI), trace concentrations below 100 ppm (m/m) are detected. By employing an ATR element of the cylindrical shape, sensors can be realized with a smooth surface ideally suited for an automatic cleaning system in a process environment. A laboratory setup with sapphire tubes as ATR elements for incorporation in a liquid flow system is described. Reflection and transmission configurations were investigated. Measurements with acetonitrile as a less toxic substitute showed that with cylindrical ATR sensors' detection limits for isocyanate concentrations below 100 ppm (m/m) are feasible.
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PMID:Cylindrical IR-ATR Sensors for Process Analytics. 3245 67