{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T05:14:45Z","timestamp":1791090885668,"version":"4.1.0"},"reference-count":36,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2018,1,2]],"date-time":"2018-01-02T00:00:00Z","timestamp":1514851200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2018,1,2]],"date-time":"2018-01-02T00:00:00Z","timestamp":1514851200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"funder":[{"name":"PSMMC-Riyadh-Saudi Arabia","award":["FJH-PSMMC"],"award-info":[{"award-number":["FJH-PSMMC"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2018,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Fabry disease (FD) is a multi\u2010systemic X\u2010linked lysosomal disorder caused by the deficient activity of \u03b1\u2010galactosidase\u2010A 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\u2010Gb<jats:sub>3<\/jats:sub>) 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\u2010Gb<jats:sub>3<\/jats:sub> levels in N215S cardiac variant FD patients. Thirty\u2010four FD patients with the late\u2010onset N215S cardiac variant mutation were enrolled along with 62 classical FD patients and 109 healthy controls. Plasma and urinary Lyso\u2010Gb<jats:sub>3<\/jats:sub> and its analogues were analyzed by LC\u2010MS\/MS. Both FD males and females with N215S mutation showed Lyso\u2010Gb<jats:sub>3<\/jats:sub> levels of (mean\u2009\u00b1\u2009SEM) 9.7\u2009\u00b1\u20091.0 and 5.4\u2009\u00b1\u20090.8 nM, respectively. These levels were significantly higher than healthy control and lower than classical FD patients (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001). Plasma Lyso\u2010Gb<jats:sub>3<\/jats:sub> levels equal to or higher than 2.7 nM yielded a diagnostic sensitivity and specificity of 100% (AUC\u2009=\u20091, p\u2009&lt;\u20090.0001). Cardiac involvement was frequent with 16\/34 (47%) developing left ventricular hypertrophy. Three patients who underwent renal biopsy had the characteristic sphingolipid deposition in the podocytes while 6\/19 (32%) had evidence of white matter changes or infarct on brain MRI. Taken together, cardiac variant N215S mutation is rather an attenuated form of classical FD. Plasma Lyso\u2010Gb<jats:sub>3<\/jats:sub> is a diagnostic hallmark to differentiate N215S variant phenotype from subjects with no FD.<\/jats:p>","DOI":"10.1007\/s10545-017-0127-2","type":"journal-article","created":{"date-parts":[[2018,1,2]],"date-time":"2018-01-02T15:35:04Z","timestamp":1514907304000},"page":"239-247","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Globotriaosylsphingosine (Lyso\u2010Gb<sub>3<\/sub>) as a biomarker for cardiac variant (N215S) Fabry disease"],"prefix":"10.1002","volume":"41","author":[{"given":"Fahad J.","family":"Alharbi","sequence":"first","affiliation":[{"name":"Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences University of Birmingham B15 2TT Birmingham UK"},{"name":"NBS &amp; Metabolic Laboratory Prince Sultan Military Medical City PO Box 7898 Riyadh 11159 Saudi 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