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Orphanet Journal of Rare Diseases
Published in: Orphanet Journal of Rare Diseases 1/2023

Open Access 01-12-2023 | Wilson's Disease | Research

Metabolomic profiling of Wilson disease, an inherited disorder of copper metabolism, and diseases with similar symptoms but normal copper metabolism

Authors: Yijie Qiu, Mingchuan Su, Xina Xiao, Dingzi Zhou, Linshen Xie

Published in: Orphanet Journal of Rare Diseases | Issue 1/2023

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Abstract

Background

Wilson’s disease (WD) is a hereditary disorder that results in the accumulation of copper. The pathogenic mechanism is not well understood, and diagnosing the disease can be challenging, as it shares similarities with more prevalent conditions. To explore the metabolomic features of WD and differentiate it from other diseases related to copper metabolism, we conducted targeted and untargeted metabolomic profiling using ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and liquid chromatography-tandem mass spectrometry (LC-MS). We compared the metabolomic profiles of two subgroups of WD patients, namely hepatic WD (H-WD) and neurological WD (N-WD), H-WD patients and liver cirrhosis patients (who exhibit similar symptoms but have normal copper levels), and N-WD patients and Parkinson’s disease patients (who exhibit similar symptoms but have normal copper levels).

Results

Our pairwise comparisons revealed distinct metabolomic profiles for male and female WD patients, H-WD and N-WD patients, N-WD and Parkinson’s disease patients, and H-WD and liver cirrhosis patients. We then employed logistic regression analysis, receiver operating characteristic (ROC) analysis, and model construction to identify candidate diagnostic biomarkers that differentiate H-WD from liver cirrhosis and N-WD from Parkinson’s disease. Based on the spatial distribution of data obtained via PLS-DA analysis, we discovered variations in hydrophilic metabolites (aminoacyl-tRNA biosynthesis; alanine, aspartate, and glutamate metabolism; phenylalanine metabolism; arginine biosynthesis; and nicotinate and nicotinamide) and lipophilic metabolites (TG(triglyceride) (16:0_16:1_22:6), TG (16:0_16:0_22:6), and TG (16:0_16:1_22:5)) between H-WD and N-WD. Moreover, WD patients display metabolic traits that distinguish it from comparable conditions (liver cirrhosis and Parkinson’s disease).

Conclusions

Our analysis reveals significant variations in the levels of metabolites in critical metabolic pathways and numerous lipids in WD.ROC analysis indicates that three metabolites may be considered as candidate biomarkers for diagnosing WD.
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Metadata
Title
Metabolomic profiling of Wilson disease, an inherited disorder of copper metabolism, and diseases with similar symptoms but normal copper metabolism
Authors
Yijie Qiu
Mingchuan Su
Xina Xiao
Dingzi Zhou
Linshen Xie
Publication date
01-12-2023
Publisher
BioMed Central
Published in
Orphanet Journal of Rare Diseases / Issue 1/2023
Electronic ISSN: 1750-1172
DOI
https://doi.org/10.1186/s13023-023-02900-5

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