title: Analysis of lyso-globotriaosylsphingosine in dried blood spots.
abstract: Recently, lyso-globotriaosylsphingosine (lyso-Gb3) was found to be elevated in plasma of treatment naive male patients and some female patients with Fabry Disease (FD). This study tested whether lyso-Gb3 could be analyzed in dried blood spots (DBS) from filter cards and whether concentrations are elevated in newborn infants with FD. Lyso-Gb3 concentrations were analyzed in DBS following extraction using a novel HPLC-mass spectrometry (MS)/MS method. Lyso-Gb3 levels in DBS were above the lower limit of quantitation (0.28 ng/mL) in 5/17 newborn FD infants (16 males; range: 1.02-8.81 ng/mL), but in none of the newborn controls, in all 13 patients (4 males) with classic FD (range: 2.06-54.1 ng/mL), in 125/159 Taiwanese individuals with symptomatic or asymptomatic FD who carry the late onset α-galactosidase A (GLA) mutation c.936+919G>A (IVS4+919G>A) (3.75±0.69 ng/mL; range: 0.418-3.97 ng/mL) and in 20/29 healthy controls (0.77±0.24 ng/mL; range: 0.507-1.4 ng/mL). The HPLC-MS/MS method for analysis of lyso-Gb3 is robust and yields reproducible results in DBS in patients with FD. However, concentrations of lyso-Gb3 were below the limit of quantitation in most newborn infants with FD rendering this approach not suitable for newborn screening. In addition, most females with the late onset mutation have undetectable lyso-Gb3 concentrations.
authors.affiliation: Division of Clinical and Translational Genetics, Department of Human Genetics, University of Miami-Miller School of Medicine, 1501 NW 10th Ave, Miami, FL 33136, USA.
authors.forename: Britt
authors.initials: B
authors.lastname: Johnson
authors.forename: Hermann
authors.initials: H
authors.lastname: Mascher
authors.forename: Daniel
authors.initials: D
authors.lastname: Mascher
authors.forename: Elisa
authors.initials: E
authors.lastname: Legnini
authors.forename: Christina Y
authors.initials: CY
authors.lastname: Hung
authors.forename: Angela
authors.initials: A
authors.lastname: Dajnoki
authors.forename: Yin-Hsiu
authors.initials: YH
authors.lastname: Chien
authors.forename: László
authors.initials: L
authors.lastname: Maródi
authors.forename: Wuh-Liang
authors.initials: WL
authors.lastname: Hwu
authors.forename: Olaf A
authors.initials: OA
authors.lastname: Bodamer
mesh_terms: D000293:Adolescent; D000328:Adult; D001774:Blood Chemical Analysis / Q000379:methods*; D002648:Child; D002851:Chromatography, High Pressure Liquid; D059788:Dried Blood Spot Testing; D000795:Fabry Disease / Q000097:blood / Q000175:diagnosis; D005260:Female; D006017:Glycolipids / Q000097:blood*; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D013107:Sphingolipids / Q000097:blood*; D053719:Tandem Mass Spectrometry; D055815:Young Adult
chemical_list: D006017:Glycolipids; D013107:Sphingolipids; C063288:globotriaosyl lysosphingolipid
keywords: Dried blood spot; Fabry disease; Filter card; Tandem mass spectrometry