Albina Nowak1, Thomas P Mechtler2, Robert J Desnick3, David C Kasper4. 1. Department of Internal Medicine, University Hospital Zurich and University of Zurich, Rämistrasse 100, 8091 Zürich, Switzerland. Electronic address: albina.nowak@usz.ch. 2. ARCHIMED Life Science, Leberstrasse 20, 1110 Vienna, Austria. Electronic address: t.mechtler@archimedlife.com. 3. Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, USA. Electronic address: robert.desnick@mssm.edu. 4. ARCHIMED Life Science, Leberstrasse 20, 1110 Vienna, Austria. Electronic address: d.kasper@archimedlife.com.
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.
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 FDpatients, 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.
Authors: Álvaro Arbeláez-Cortés; Diana C Quintero-González; Yesid Cuesta-Astroz; Juan S Villadiego; Herman González-Buriticá; Jorge M Rueda Journal: Rheumatol Int Date: 2019-10-10 Impact factor: 2.631
Authors: Cassiano Augusto Braga Silva; Luis Gustavo Modelli de Andrade; Maria Helena Vaisbich; Fellype de Carvalho Barreto Journal: J Bras Nefrol Date: 2022 Apr-Jun
Authors: Daniel Franzen; Sarah R Haile; David C Kasper; Thomas P Mechtler; Andreas J Flammer; Pierre A Krayenbühl; Albina Nowak Journal: BMJ Open Respir Res Date: 2018-04-21