Levels of enzyme activities in six lysosomal storage diseases in Japanese neonates determined by liquid chromatography-tandem mass spectrometry

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• 作者：Ryuichi Mashima^a ; ^{mashima-r@ncchd.go.jp} ; Eri Sakai^a ; Motomichi Kosuga^a ; ^b ; ^c ; Torayuki Okuyama^a ; ^b
• 刊名：Molecular Genetics and Metabolism Reports
• 出版年：2016
• 出版时间：December 2016
• 年：2016
• 卷：9
• 期：Complete
• 页码：6-11
• 全文大小：541 K
• 卷排序：9

文摘

Lysosomal storage disorders (LSDs) are caused by defective enzyme activities in lysosomes, characterized by the accumulation of glycolipids, oligosaccharides, mucopolysaccharides, sphingolipids, and other biological substances. Accumulating evidence has suggested that early detection of individuals with LSDs, followed by the immediate initiation of appropriate therapy during the presymptomatic period, usually results in better therapeutic outcomes. The activities of individual enzymes are measured using fluorescent substrates. However, the simultaneous determination of multiple enzyme activities has been awaited in neonatal screening of LSDs because the prevalence of individual LSDs is rare. In this study, the activities of six enzymes associated with LSDs were examined with 6-plex enzyme assay using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The accumulation of enzyme products was almost linear for 0–20 h at 37 °C. Dried blood spots (DBSs) provided by the Centers for Disease Control and Prevention (CDC) were used for quality control (QC). The intraday and interday coefficient of variance values were < 25%. The enzyme activities of healthy individuals were higher than those of LSD-confirmed individuals. These results suggest that the levels of enzyme activities of six LSDs in a Japanese population were comparable to those of a recent report [Elliott et al. Mol Genet Metab 118 (2016) 304–309], providing additional evidence that the 6-plex LSD enzyme assay is a reproducible analytical procedure for neonatal screening.