Polycystic Kidneys and GM<sub>2</sub>Gangliosidosis-Like Disease in Neonatal Springboks (<i>Antidorcas marsupialis</i>)

Herder, Vanessa; Kummrow, Maya; Leeb, Tosso; Sewell, A. C.; Hansmann, Florian; Lehmbecker, Annika; Wohlsein, P.; Baumgärtner, Wolfgang

doi:10.1177/0300985814549210

Cited by 6 publications

(1 citation statement)

References 61 publications

(114 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Indeed, creatine in dietary meat is chemically transformed to Cn during high temperature cooking processes [112], and is readily absorbed following ingestion, a process conceivably reinforcing and enhancing plasma Cn levels. Interestingly, Herder et al [113] discovered that springbok antelopes with a GM2 gangliosidosis disorder resembling hu-man Sandhoff disease also presented with polycystic kidney disease-human patients with the latter condition typically display high plasma/serum Cn concentrations [114]. Although this finding may be incidental, there remains the possibility of a genetic association between these two conditions.…”

Section: Potential Limitations Of the Studymentioning

confidence: 99%

Rapid Identification of New Biomarkers for the Classification of GM1 Type 2 Gangliosidosis Using an Unbiased 1H NMR-Linked Metabolomics Strategy

Percival

Latour

Tifft

et al. 2021

Cells

View full text Add to dashboard Cite

Biomarkers currently available for the diagnosis, prognosis, and therapeutic monitoring of GM1 gangliosidosis type 2 (GM1T2) disease are mainly limited to those discovered in targeted proteomic-based studies. In order to identify and establish new, predominantly low-molecular-mass biomarkers for this disorder, we employed an untargeted, multi-analyte approach involving high-resolution 1H NMR analysis coupled to a range of multivariate analysis and computational intelligence technique (CIT) strategies to explore biomolecular distinctions between blood plasma samples collected from GM1T2 and healthy control (HC) participants (n = 10 and 28, respectively). The relationship of these differences to metabolic mechanisms underlying the pathogenesis of GM1T2 disorder was also investigated. 1H NMR-linked metabolomics analyses revealed significant GM1T2-mediated dysregulations in ≥13 blood plasma metabolites (corrected p < 0.04), and these included significant upregulations in 7 amino acids, and downregulations in lipoprotein-associated triacylglycerols and alanine. Indeed, results acquired demonstrated a profound distinctiveness between the GM1T2 and HC profiles. Additionally, employment of a genome-scale network model of human metabolism provided evidence that perturbations to propanoate, ethanol, amino-sugar, aspartate, seleno-amino acid, glutathione and alanine metabolism, fatty acid biosynthesis, and most especially branched-chain amino acid degradation (p = 10−12−10−5) were the most important topologically-highlighted dysregulated pathways contributing towards GM1T2 disease pathology. Quantitative metabolite set enrichment analysis revealed that pathological locations associated with these dysfunctions were in the order fibroblasts > Golgi apparatus > mitochondria > spleen ≈ skeletal muscle ≈ muscle in general. In conclusion, results acquired demonstrated marked metabolic imbalances and alterations to energy demand, which are consistent with GM1T2 disease pathogenesis mechanisms.

show abstract

Section: Potential Limitations Of the Studymentioning

confidence: 99%