Background: Fabry disease (FD) is a rare X-linked lysosomal storage disorder due to mutations in the a-galactosidase A gene (GLA) that result in absent or markedly reduce a-galactosidase A (a-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 a-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 a-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 a-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.

Published in Molecular Genetics and Metabolism.
Read the full publication about Plasma_LysoGb3_A_useful_biomarker_for_the_diagnosis_fabry_disease

Authors / *corresponding author

*Albina Nowak,a, Thomas P. Mechtler, b, Robert J.Desnick, c, David C. Kasper,b
a Department of Internal Medicine, University Hospital Zurich and University of Zurich, Rämistrasse 100, 8091 Zürich, Switzerland;
b ARCHIMED Life Science, Leberstrasse 20, 1110 Vienna, Austria;;
c Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, USA;