Christiane Auray-Blais1, Pamela Lavoie2, Michel Boutin2, Aimé Ntwari2, Ting-Rong Hsu3, Chun-Kai Huang4, Dau-Ming Niu3. 1. Division of Medical Genetics, Department of Pediatrics, Faculty of Medicine and Health Sciences, Université de Sherbrooke, 3001, 12th Avenue North, Sherbrooke, QC J1H 5N4, Canada. Electronic address: christiane.auray-blais@usherbrooke.ca. 2. Division of Medical Genetics, Department of Pediatrics, Faculty of Medicine and Health Sciences, Université de Sherbrooke, 3001, 12th Avenue North, Sherbrooke, QC J1H 5N4, Canada. 3. Department of Pediatrics, Taipei Veterans General Hospital, Taipei, Taiwan, ROC; Institute of Clinical Medicine, National Yang-Ming University, School of Medicine, Taipei, Taiwan, ROC. 4. Department of Pediatrics, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
Abstract
BACKGROUND: Fabry disease is a lysosomal storage disorder with an incidence of 1:1600 for the late-onset IVS4+919G>A cardiac variant mutation in Taiwan. Signs and symptoms of this cardiac variant include left ventricular hypertrophy, mitral insufficiency and/or arrhythmias. The search for biomarkers that might predict the clinical outcomes and guide treatment options is important. We thus investigated relationships between Fabry disease biomarkers (such as globotriaosylceramide (Gb3), globotriaosylsphingosine (lyso-Gb3)/related analogues) and age, gender, enzyme activity, clinical manifestations and severity of the disease in these patients. METHOD: Urine and plasma biomarkers were analyzed using tandem mass spectrometry. A large cohort of 191 adult and pediatric Fabry patients carrying the IVS4+919G>A mutation was studied. Some patients were members of the same family. RESULTS: Our results show that the plasma lyso-Gb3 level, and urinary analogue levels of lyso-Gb3 at m/z (+16), (+34), and (+50) adjusted for gender and age had a positive association with the left ventricular mass index, and/or the Mainz Severity Score Index. CONCLUSIONS: It might thus be of particular interest to monitor children with high levels of these biomarkers, as part of a longitudinal study in order to determine if the excretion profile at a young age is predictive of the outcomes of disease severity in adulthood.
BACKGROUND:Fabry disease is a lysosomal storage disorder with an incidence of 1:1600 for the late-onset IVS4+919G>A cardiac variant mutation in Taiwan. Signs and symptoms of this cardiac variant include left ventricular hypertrophy, mitral insufficiency and/or arrhythmias. The search for biomarkers that might predict the clinical outcomes and guide treatment options is important. We thus investigated relationships between Fabry disease biomarkers (such as globotriaosylceramide (Gb3), globotriaosylsphingosine (lyso-Gb3)/related analogues) and age, gender, enzyme activity, clinical manifestations and severity of the disease in these patients. METHOD: Urine and plasma biomarkers were analyzed using tandem mass spectrometry. A large cohort of 191 adult and pediatric Fabry patients carrying the IVS4+919G>A mutation was studied. Some patients were members of the same family. RESULTS: Our results show that the plasma lyso-Gb3 level, and urinary analogue levels of lyso-Gb3 at m/z (+16), (+34), and (+50) adjusted for gender and age had a positive association with the left ventricular mass index, and/or the Mainz Severity Score Index. CONCLUSIONS: It might thus be of particular interest to monitor children with high levels of these biomarkers, as part of a longitudinal study in order to determine if the excretion profile at a young age is predictive of the outcomes of disease severity in adulthood.
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Authors: Aizeddin A Mhanni; Christiane Auray-Blais; Michel Boutin; Alie Johnston; Kaye LeMoine; Jill Patterson; Johannes M F G Aerts; Michael L West; Cheryl Rockman-Greenberg Journal: Mol Genet Metab Rep Date: 2020-06-24