• Fahad J Alharbi, Shanat Baig, Srinivasa B Rambhatla, Ravi Vijapurapu, Christiane Auray-Blais, Michel Boutin, Richard Steeds, Nigel Wheeldon, Charlotte Dawson, and Tarekegn Geberhiwot.
• Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK; NBS & Metabolic Laboratory, Prince Sultan Military Medical City, PO Box 7897, Riyadh 11159, Saudi Arabia. Electronic address: fjharbi@psmmc.med.sa.
• Clin. Chim. Acta. 2020 Jan 1; 500: 120-127.

BackgroundFabry disease (FD) is a genetic disorder caused by defective α-galactosidase-A enzyme due to mutations in the GLA gene. A reliable diagnosis in classical FD males can be made by measuring the enzyme activity while diagnosing classical FD females and non-classical FD patients requires mutation analysis. Plasma globotriaosylsphingosine (Lyso-Gb3) has progressively gained more importance as a diagnostic biomarker for FD in recent years. Having another biomarker to complement plasma Lyso-Gb3 will increase the diagnostic accuracy in the era of mass screening, and also precision medicine. This study aims to highlight the clinical utility of the total concentration of urinary Lyso-Gb3 plus its analogues in diagnosing FD.MethodRandom urine samples collected from 42 FD patients and 48 healthy individuals. Lyso-Gb3 and its analogues were enriched by solid phase extraction and analysed by liquid chromatography tandem mass spectrometry.ResultsThe total concentration of Lyso-Gb3 plus its analogues in classical FD male and female patients were 1124.4 ± 181.2 and 308.6 ± 78.6 pmol/mmol creat., respectively. The levels in non-classical FD male and female patients were 229.2 ± 169.4 and 314.4 ± 156.4 pmol/mmol creat., respectively. Urinary Lyso-Gb3 and its analogues were virtually undetectable in healthy volunteers making it 100% specific for FD diagnosis. For FD male and female patients, total concentration of urinary Lyso-Gb3 plus its analogue levels ≥0.25 pmol/mmol creat. yielded a diagnostic sensitivity and specificity of 100% (AUC = 1, p < 0.00001).ConclusionsOur study findings support that the total concentration of Lyso-Gb3 plus its analogues in urine is specific to FD and may provide extra diagnostic utility for both classical and non-classical FD patients.Copyright © 2019 Elsevier B.V. All rights reserved.

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