LC-MS Based Platform Simplifies Access to Metabolomics for Peroxisomal Disorders

Klemp, Henry Gerd; Kettwig, Matthias; Streit, Frank; Gärtner, Jutta; Rosewich, Hendrik; Krätzner, Ralph

doi:10.3390/metabo11060347

Cited by 2 publications

(1 citation statement)

References 30 publications

(41 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…First introduced in 2013, newborn screening for X-ALD is now carried out in 20 States and the District of Columbia with 2 additional states currently running pilot programs (https:// adrenoleukodystrophy.info/clinical-diagnosis/ald-newbornscreening). Therefore, every newborn from these states will have C26:0-LPC testing at birth, which will identify all newborns with PBD-ZSD (Klemp et al, 2021). Concerns have been raised around the "incidental" identification of PBD-ZSD patients through the X-ALD screening due to lack of targeted treatment that modifies the course of PBD-ZSD.…”

Section: Gene Mutations In Peroxisomal Biogenesismentioning

confidence: 99%

Dysfunctional peroxisomal lipid metabolisms and their ocular manifestations

Chen

Shao²,

Fu³

2022

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Retina is rich in lipids and dyslipidemia causes retinal dysfunction and eye diseases. In retina, lipids are not only important membrane component in cells and organelles but also fuel substrates for energy production. However, our current knowledge of lipid processing in the retina are very limited. Peroxisomes play a critical role in lipid homeostasis and genetic disorders with peroxisomal dysfunction have different types of ocular complications. In this review, we focus on the role of peroxisomes in lipid metabolism, including degradation and detoxification of very-long-chain fatty acids, branched-chain fatty acids, dicarboxylic acids, reactive oxygen/nitrogen species, glyoxylate, and amino acids, as well as biosynthesis of docosahexaenoic acid, plasmalogen and bile acids. We also discuss the potential contributions of peroxisomal pathways to eye health and summarize the reported cases of ocular symptoms in patients with peroxisomal disorders, corresponding to each disrupted peroxisomal pathway. We also review the cross-talk between peroxisomes and other organelles such as lysosomes, endoplasmic reticulum and mitochondria.

show abstract

Section: Gene Mutations In Peroxisomal Biogenesismentioning

confidence: 99%

Dysfunctional peroxisomal lipid metabolisms and their ocular manifestations

Chen

Shao²,

Fu³

2022

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

show abstract

Multivariate analysis and model building for classifying patients in the peroxisomal disorders X-linked adrenoleukodystrophy and Zellweger syndrome in Chinese pediatric patients

Zhu

Genchev

Wang

et al. 2023

Orphanet J Rare Dis

View full text Add to dashboard Cite

Background The peroxisome is a ubiquitous single membrane-enclosed organelle with an important metabolic role. Peroxisomal disorders represent a class of medical conditions caused by deficiencies in peroxisome function and are segmented into enzyme-and-transporter defects (defects in single peroxisomal proteins) and peroxisome biogenesis disorders (defects in the peroxin proteins, critical for normal peroxisome assembly and biogenesis). In this study, we employed multivariate supervised and non-supervised statistical methods and utilized mass spectrometry data of neurological patients, peroxisomal disorder patients (X-linked adrenoleukodystrophy and Zellweger syndrome), and healthy controls to analyze the role of common metabolites in peroxisomal disorders, to develop and refine a classification models of X-linked adrenoleukodystrophy and Zellweger syndrome, and to explore analytes with utility in rapid screening and diagnostics. Results T-SNE, PCA, and (sparse) PLS-DA, operated on mass spectrometry data of patients and healthy controls were utilized in this study. The performance of exploratory PLS-DA models was assessed to determine a suitable number of latent components and variables to retain for sparse PLS-DA models. Reduced-features (sparse) PLS-DA models achieved excellent classification performance of X-linked adrenoleukodystrophy and Zellweger syndrome patients. Conclusions Our study demonstrated metabolic differences between healthy controls, neurological patients, and peroxisomal disorder (X-linked adrenoleukodystrophy and Zellweger syndrome) patients, refined classification models and showed the potential utility of hexacosanoylcarnitine (C26:0-carnitine) as a screening analyte for Chinese patients in the context of a multivariate discriminant model predictive of peroxisomal disorders.

show abstract

LC-MS Based Platform Simplifies Access to Metabolomics for Peroxisomal Disorders

Cited by 2 publications

References 30 publications

Dysfunctional peroxisomal lipid metabolisms and their ocular manifestations

Dysfunctional peroxisomal lipid metabolisms and their ocular manifestations

Multivariate analysis and model building for classifying patients in the peroxisomal disorders X-linked adrenoleukodystrophy and Zellweger syndrome in Chinese pediatric patients

Contact Info

Product

Resources

About