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

Published on Jan 1, 2017in Molecular Genetics and Metabolism4.17
· DOI :10.1016/J.YMGME.2016.10.006
Albina Nowak15
Estimated H-index: 15
(UZH: University of Zurich),
Thomas P. Mechtler14
Estimated H-index: 14
+ 1 AuthorsDavid C. Kasper22
Estimated H-index: 22
Abstract Background 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. Methods Among 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. Results We identified three unrelated females in whom the accumulating LysoGb3 was increased, whereas their leukocyte α-GalA activities were in the normal range. Conclusion LysoGb3 serves as an useful biomarker to improve the diagnosis of FD heterozygotes and for therapeutic evaluation and monitoring.
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