Globotriaosylsphingosine (Lyso-Gb3) as a biomarker for cardiac variant (N215S) Fabry disease

• Published in: Journal of inherited metabolic disease 2018-03, Vol.41 (2), p.239-247
• Main Authors: Alharbi, Fahad J., Baig, Shanat, Auray-Blais, Christiane, Boutin, Michel, Ward, Douglas G., Wheeldon, Nigel, Steed, Rick, Dawson, Charlotte, Hughes, Derralynn, Geberhiwot, Tarekegn
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; alpha-Galactosidase - genetics; alpha-Galactosidase - metabolism; Biochemistry; Biomarkers - blood; Biomarkers - urine; Biopsy; Case-Control Studies; Coronary artery disease; Enzyme Replacement Therapy; Fabry Disease - blood; Fabry Disease - diagnosis; Fabry Disease - genetics; Fabry Disease - urine; Fabry's disease; Female; Genetic Predisposition to Disease; Glycolipids - blood; Glycolipids - urine; Glycosphingolipids; Heart diseases; Human Genetics; Humans; Hypertrophy; Internal Medicine; Kidneys; Magnetic resonance imaging; Male; Medicine; Medicine & Public Health; Metabolic Diseases; Middle Aged; Mutation; Original Article; Pediatrics; Phenotype; Plasma; Predictive Value of Tests; Sphingolipids - blood; Sphingolipids - urine; Substantia alba; Up-Regulation; Ventricle; Young Adult
• ISSN: 0141-8955; 1573-2665
• DOI: 10.1007/s10545-017-0127-2

Fabry disease (FD) is a multi-systemic X-linked lysosomal disorder caused by the deficient activity of α-galactosidase-A enzyme, which leads to accumulation of glycosphingolipids in various body tissues. The N215S mutation is a known variant of FD, with a late onset cardiac phenotype. Consensus guidelines acknowledged the use of globotriaosylsphingosine (Lyso-Gb 3 ) as a diagnostic marker for classical FD but its utility for cardiac variant FD is not clear. We aim to characterize the clinical features and evaluate the diagnostic accuracy of plasma and urinary Lyso-Gb 3 levels in N215S cardiac variant FD patients. Thirty-four FD patients with the late-onset N215S cardiac variant mutation were enrolled along with 62 classical FD patients and 109 healthy controls. Plasma and urinary Lyso-Gb 3 and its analogues were analyzed by LC-MS/MS. Both FD males and females with N215S mutation showed Lyso-Gb 3 levels of (mean ± SEM) 9.7 ± 1.0 and 5.4 ± 0.8 nM, respectively. These levels were significantly higher than healthy control and lower than classical FD patients ( p