Summary of project PR000281

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench,, where it has been assigned Project ID PR000281. The data can be accessed directly via it's Project DOI: 10.21228/M8KW38 This work is supported by NIH grant, U2C- DK119886.


Project ID: PR000281
Project DOI:doi: 10.21228/M8KW38
Project Title:Metabolic profiling reveals biochemical pathways and potential biomarkers associated with the pathogenesis of Krabbe disease
Project Type:Disease Profiling
Project Summary:Krabbe disease (KD) is caused by mutations in the galactosylceramidase (GALC) gene, which encodes a lysosomal enzyme that degrades galactolipids, including galactosylceramide and galactosylsphingosine (psychosine). GALC deficiency results in progressive intracellular accumulation of psychosine, which is believed to be the main cause for the demyelinating neurodegeneration in KD pathology. Umbilical cord blood transplantation slows disease progression if performed presymptomatically, but carries a significant risk of morbidity and mortality. Accurate presymptomatic diagnosis is therefore critical to facilitate the efficacy of existing transplant approaches and avoid unnecessary treatment of children who will not develop KD. Unfortunately current diagnostic criteria, including GALC activity, genetic analysis, and psychosine measurement, are insufficient for secure presymptomatic diagnosis. Herein, we performed a global metabolomic analysis to identify pathogenetic metabolic pathways and novel biomarkers implicated in the authentic mouse model of KD, twitcher. At a time point before onset of signs of disease, twitcher hindbrains had metabolic profiles similar to wild type, with the exception of a decrease in metabolites related to glucose energy metabolism. Instead, many metabolic pathways were altered after early signs of disease in the twitcher, including decreased phospholipid turnover, restricted mitochondrial metabolism of branched-chain amino acids, increased inflammation, neurotransmitter metabolism and osmolytes. Hypoxanthine, a purine derivative, is increased before signs of disease appear, suggesting its potential as a biomarker for early diagnosis of KD. Additionally, given the early changes in glucose metabolism in the pathogenesis of KD, diagnostic modalities that report metabolic function, such as positron emission tomography, may be useful in KD.
Institute:University at Buffalo
Department:Hunter James Kelly Research Institute
Laboratory:Shin Laboratory
Last Name:Shin
First Name:Daesung
Address:NYS Center of Excellence in Bioinformatics & Life Sciences, 701 Ellicott Street, Buffalo, NY 14203

Summary of all studies in project PR000281

Study IDStudy TitleSpeciesInstituteAnalysis
(* : Contains Untargted data)
(* : Contains raw data)
ST000352 Metabolic profiling reveals biochemical pathways and potential biomarkers associated with the pathogenesis of Krabbe disease Mus musculus University at Buffalo MS 2016-03-03 1 32 Uploaded data (315K)*