title: Lyso-globotriaosylsphingosine (lyso-Gb3) levels in neonates and adults with the Fabry disease later-onset GLA IVS4+919G>A mutation.
abstract: Lyso-globotriaosylsphingosine (lyso-Gb3) is a useful biomarker in the diagnosis and monitoring of treatment for Fabry disease. However, it is unclear whether lyso-Gb3 is elevated in patients with later-onset Fabry disease. Thus, we measured lyso-Gb3 levels from dried blood spots (DBS) from male newborns with the Fabry disease later-onset phenotype, IVS4+919G>A mutation, and their family members. The lyso-Gb3 levels were below the detection limit in normal control newborns and were slightly higher in adults. In males of all ages with the IVS4+919G>A mutation, lyso-Gb3 levels were elevated and were higher than in age-matched controls. The elevation of lyso-Gb3 levels in males with the IVS4+919G>A mutation was only slightly elevated compared with patients with the classical Fabry phenotype. The measurement of lyso-Gb3 levels is useful in the diagnosis of Fabry disease, including the later-onset phenotype. The DBS lyso-Gb3 level was not elevated in IVS4+919G>A heterozygotes, and is not useful for their diagnosis. Since lyso-Gb3 levels are elevated from birth in Fabry disease males, "an elevated lyso-Gb3 level" may be of little values for deciding when to begin enzyme replacement therapy.
authors.affiliation: Department of Medical Genetics and Pediatrics, National Taiwan University Hospital, Taipei, Taiwan. chienyh@ntu.edu.tw
authors.forename: Yin-Hsiu
authors.initials: YH
authors.lastname: Chien
authors.forename: Olaf A
authors.initials: OA
authors.lastname: Bodamer
authors.forename: Shu-Chuan
authors.initials: SC
authors.lastname: Chiang
authors.forename: Hermann
authors.initials: H
authors.lastname: Mascher
authors.forename: Christina
authors.initials: C
authors.lastname: Hung
authors.forename: Wuh-Liang
authors.initials: WL
authors.lastname: Hwu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D000795:Fabry Disease / Q000097:blood / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D006017:Glycolipids / Q000097:blood / Q000235:genetics* / Q000378:metabolism*; D006579:Heterozygote; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D010865:Pilot Projects; D013107:Sphingolipids / Q000097:blood / Q000235:genetics* / Q000378:metabolism*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D006017:Glycolipids; D013107:Sphingolipids; C063288:globotriaosyl lysosphingolipid