Globotriaosylsphingosine (lyso-Gb) and analogues in plasma and urine of patients with Fabry disease and correlations with long-term treatment and genotypes in a nationwide female Danish cohort.

Introduction: Recent studies showed the usefulness of globotriaosylsphingosine (lyso-Gb) and related analogues, deacylated forms of globotriaosylceramide (Gb), for high-risk screening, treatment monitoring and follow-up for patients with Fabry disease.

Methods: We evaluated Gb, lyso-Gb and analogues using tandem mass spectrometry in 57 women with Fabry disease followed during a period of 15.4 years.

Diurnal Variation of Urinary Fabry Disease Biomarkers during Enzyme Replacement Therapy Cycles.

Fabry disease is an X-linked lysosomal storage disorder caused by mutations in the gene encoding the α-galactosidase A enzyme. This enzyme cleaves the last sugar unit of glycosphingolipids, including globotriaosylceramide (Gb), globotriaosylsphingosine (lyso-Gb), and galabiosylceramide (Ga). Enzyme impairment leads to substrate accumulation in different organs, vascular endothelia, and biological fluids.

Altered immune phenotypes in subjects with Fabry disease and responses to switching from agalsidase alfa to agalsidase beta.

Fabry disease (FD) is a rare X-linked genetic disorder caused by mutations in the gene encoding the lysosomal enzyme, α-galactosidase A (α-gal A). The mutations lead to lack of or faulty enzyme causing accumulation of globotriaosylceramide (Gb3) and related glycosphingolipids including globotriaosylsphingosine (lyso-Gb). Treatment options for FD include enzyme replacement therapy.

Analysis of globotriaosylceramide (Gb) isoforms/analogs in unfractionated leukocytes, B lymphocytes and monocytes from Fabry patients using ultra-high performance liquid chromatography/tandem mass spectrometry.

Fabry disease is an X-linked lysosomal storage disorder with marked variability in the phenotype and genotype. Glycosphingolipids such as globotriaosylceramide (Gb) isoforms/analogs, globotriaosylsphingosine (lyso-Gb) and analogs, and galabiosylceramide (Ga) isoforms/analogs may accumulate in biological fluids and different organs. The aims of this study were to: 1) develop/validate a novel UHPLC-MS/MS method for relative quantitation of Gb in leukocytes (unfractionated white blood cells), B lymphocytes and monocytes; 2) evaluate these biomarkers in a cohort of Fabry patients and healthy controls; and 3) assess correlations between these biomarkers, treatment and genotype.

Lentivector Iterations and Pre-Clinical Scale-Up/Toxicity Testing: Targeting Mobilized CD34 Cells for Correction of Fabry Disease.

Fabry disease is a rare lysosomal storage disorder (LSD). We designed multiple recombinant lentivirus vectors (LVs) and tested their ability to engineer expression of human α-galactosidase A (α-gal A) in transduced Fabry patient CD34 hematopoietic cells. We further investigated the safety and efficacy of a clinically directed vector, LV/AGA, in both ex vivo cell culture studies and animal models.

High-Risk Screening for Fabry Disease: Analysis by Tandem Mass Spectrometry of Globotriaosylceramide (Gb ) in Urine Collected on Filter Paper.

Fabry disease is a complex, panethnic lysosomal storage disorder. It is characterized by the accumulation of glycosphingolipids in tissues, organs, the vascular endothelium, and biological fluids. The reported incidence in different populations is quite variable, ranging from 1:1400 to 1:117,000.

High-Risk Screening of Fabry Disease: Analysis of Fifteen Urinary Methylated and Non-Methylated Gb Isoforms Using Tandem Mass Spectrometry.

Fabry disease is a multisystemic, X-linked lysosomal storage disorder caused by mutations in the GLA gene, leading to α-galactosidase A deficiency and resulting in the accumulation of glycosphingolipids in different tissues and biological fluids. Glycosphingolipid biomarkers, such as globotriaosylceramide (Gb ) isoforms, globotriaosylsphingosine (lyso-Gb ) and related analogs, and galabiosylceramide (Ga ) isoforms and analogs, are found to be abnormally increased in urine and in plasma of Fabry patients and have the potential to be used as specific biomarkers of the disease. This unit presents a protocol for the relative quantification of fifteen urinary isoforms of Gb analyzed simultaneously with creatinine by ultra-performance liquid chromatography (UPLC) coupled to tandem mass spectrometry (MS/MS).

Tandem Mass Spectrometry Quantitation of Lyso-Gb3 and Six Related Analogs in Plasma for Fabry Disease Patients.

Fabry disease is an X-linked lysosomal storage disorder, caused by a deficit in α-galactosidase A enzyme activity, leading to the storage of sphingolipids such as globotriaosylsphingosine (lyso-Gb3 ), globotriaosylceramide (Gb3 ), and galabiosylceramide (Ga2 ) in organs, tissues and biological fluids. A recent metabolomic study performed in plasma revealed lyso-Gb3 analogs as novel Fabry disease biomarkers. These molecules correspond to lyso-Gb3 with different chemical modifications on the sphingosine chain (-C2 H4 , -H2 , +O, +H2 O, +H2 O2, and +H2 O3 ).

Fabry Disease Biomarkers: Analysis of Urinary Lyso-Gb3 and Seven Related Analogs Using Tandem Mass Spectrometry.

Fabry disease is an X-linked lysosomal storage disorder caused by the absence or reduction of the enzyme α-galactosidase A activity. Currently, globotriaosylsphingosine (lyso-Gb3 ) and globotriaosylceramide (Gb3 ) are used as biomarkers to diagnose and monitor Fabry patients. However, recent metabolomic studies have shown that several glycosphingolipids are also elevated in biological fluids of affected patients and may be related to disease manifestations.

Tandem mass spectrometry multiplex analysis of methylated and non-methylated urinary Gb3 isoforms in Fabry disease patients.

Background: Fabry disease is a lysosomal storage disorder leading to the accumulation of glycosphingolipids in biological fluids and tissues. Globotriaosylceramide (Gb3) and globotriaosylsphingosine (lyso-Gb3) are currently used for Fabry screening and diagnosis. However, these biomarkers are not always increased in Fabry patients with residual enzyme activity.