Plasma LysoGb3: A useful biomarker for the diagnosis and treatment of Fabry disease heterozygotes

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• 作者：Albina Nowak^a ; ^{albina.nowak@usz.ch} ; Thomas P. Mechtler^b ; ^{t.mechtler@archimedlife.com} ; Robert J. Desnick^c ; ^{robert.desnick@mssm.edu} ; David C. Kasper^b ; ^{d.kasper@archimedlife.com}
• 关键词：Fabry disease ; Heterozygotes ; LysoGb3 ; Biomarker ; α-galactosidase deficiency
• 刊名：Molecular Genetics and Metabolism
• 出版年：2017
• 出版时间：January-February 2017
• 年：2017
• 卷：120
• 期：1-2
• 页码：57-61
• 全文大小：652 K
• 卷排序：120

文摘

Fabry disease (FD) is a rare X-linked lysosomal storage disorder due to mutations in the α-galactosidase A gene (GLA) that result in absent or markedly reduce α-galactosidase A (α-GalA) enzymatic activity. As a result, the major glycosphingolipid substrates, globotriaosylceramide (Gb3) and globotriaosylsphingosine (LysoGb3) accumulate in plasma, urine and tissue lysosomes. In females, the diagnosis can be complicated by the fact that 40–50% of GLA-mutation confirmed heterozygotes have normal or only slightly decreased leukocyte α-GalA activities. Recently, LysoGb3 has been appreciated as a novel FD biomarker, especially for therapeutic monitoring.MethodsAmong our GLA-mutation proven FD patients, we screened 18 heterozygotes whose leukocyte α-GalA activity was determined at initial diagnosis. For these females, we measured their serum LysoGb3 levels using highly-sensitive electrospray ionization liquid chromatography tandem mass spectrometry.ResultsWe identified three unrelated females in whom the accumulating LysoGb3 was increased, whereas their leukocyte α-GalA activities were in the normal range.ConclusionLysoGb3 serves as an useful biomarker to improve the diagnosis of FD heterozygotes and for therapeutic evaluation and monitoring.