LC-MS lipidomics of renal biopsies for the diagnosis of Fabry disease

Abstract

Highlights Fabry is an X-linked lysosomal storage disease with deficiency in α-galactosidase. This deficiency results in the accumulation of glycosphinogolipids. Diagnosis is often made by analysis of globotriaosylceramide in fluids and tissues. Fabry is often misdiagnosed in female patients due to residual enzyme activity. Lipidomics by LC-HRMS enables identification of new biomarkers in Fabry.

Quantitation of a Urinary Profile of Biomarkers in Gaucher Disease Type 1 Patients Using Tandem Mass Spectrometry

“…While these data suggest that the aforementioned metabolites may be more sensitive for patient follow-up and monitoring, we would like to emphasize that most untreated patients in our cohort had an attenuated form of the disease. Based on studies performed on other LSDs, it was demonstrated that even after treatment with ERT, residual levels of biomarkers are still present in tissues and biological fluids [ 26 ]. Patients classified as “borderline to mild” typically do not have an important concentration of biomarkers, whereas for patients who are treated, biomarkers levels never truly return to baseline values such as those observed in healthy controls.…”

“…In the past, our research group performed several metabolomic studies in urine on Fabry disease, where glycosphingolipid accumulation is also involved. These studies led to the discovery of novel lyso-Gb 3 analogs with different modifications on the sphingosine moiety [ 25 , 26 ]. Another study highlighted that several lyso-Gb 3 analogs had a significant correlation with specific clinical manifestations of the disease [ 27 ].…”

Lipidomics as a Tool in the Diagnosis and Clinical Therapy

“…Rare disorders remain a challenge even to modern medicine, and mounting evidence shows the prominent role of lipidomics in this scenario [12]. In patients with Lipidomics as a Tool in the Diagnosis and Clinical Therapy DOI: http://dx.doi.org/10.5772/intechopen.105857…”

“…Olmsted syndrome caused striking decreases in 15-LOX and dhCer levels [77]. In patients with Fabry disease, the presence of glycosphingolipids, galabiosylceramide, and globotriaosylsphingosine is observed in vascular endothelium, nerves, cardiomyocytes, and renal glomerular podocytes [12]. A dysregulation in lipids involved in both cellular structure and membrane integrity was identified in fragile X syndrome, suggesting that X chromosomal deletion disorders are not limited to alterations in neuronal functions [78].…”

“…Lipidomics is a sub-branch of metabolomics devoted to studying the complete lipid profile within a cell, tissue, or organism through spectroscopic and/or spectrometric methods in combination with bioinformatic analysis [4,9,11]. This combined approach provides a comprehensive understanding of the role of the lipid profile -the lipidome-in biological systems [12]. Thus, the stability and reproducibility of the analytical methods are critical for producing reliable output [13].…”