title: Plasma LysoGb3: A useful biomarker for the diagnosis and treatment of Fabry disease heterozygotes.
abstract: 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.
  
  
  
  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.
  
  
  
  We identified three unrelated females in whom the accumulating LysoGb3 was increased, whereas their leukocyte α-GalA activities were in the normal range.
  
  
  
  LysoGb3 serves as an useful biomarker to improve the diagnosis of FD heterozygotes and for therapeutic evaluation and monitoring.
authors: Department of Internal Medicine, University Hospital Zurich and University of Zurich, Rämistrasse 100, 8091 Zürich, Switzerland. Electronic address: albina.nowak@usz.ch.
authors: Albina
authors: A
authors: Nowak
authors: ARCHIMED Life Science, Leberstrasse 20, 1110 Vienna, Austria. Electronic address: t.mechtler@archimedlife.com.
authors: Thomas P
authors: TP
authors: Mechtler
authors: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, USA. Electronic address: robert.desnick@mssm.edu.
authors: Robert J
authors: RJ
authors: Desnick
authors: ARCHIMED Life Science, Leberstrasse 20, 1110 Vienna, Austria. Electronic address: d.kasper@archimedlife.com.
authors: David C
authors: DC
authors: Kasper
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood*; D002648:Child; D002853:Chromatography, Liquid; D000795:Fabry Disease / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D005260:Female; D006017:Glycolipids / Q000097:blood*; D006579:Heterozygote; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D021241:Spectrometry, Mass, Electrospray Ionization; D013107:Sphingolipids / Q000097:blood*; D000519:alpha-Galactosidase / Q000097:blood / Q000235:genetics*
chemical_list: D015415:Biomarkers; D006017:Glycolipids; D013107:Sphingolipids; C063288:globotriaosyl lysosphingolipid; C576330:GLA protein, human; D000519:alpha-Galactosidase
keywords: Biomarker; Fabry disease; Heterozygotes; LysoGb3; α-galactosidase deficiency