Evidence map›Paper›PMID 41454338›Full record

ArticleOrphanet journal of rare diseases2025

Discovery of newborn Wilson disease biomarkers via integrated next-generation sequencing and untargeted metabolomics.

Xianwei Guan, Yun Sun, Yanyun Wang, Yahong Li, Zhilei Zhang, Dongyang Hong, Peiying Yang, Xiaowei Liang, Xin Wang, Bin Yu

Abstract read
In one paragraph

Article in Orphanet journal of rare diseases, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Xianwei GuanGenetic Medicine Center, Women's Hospital of Nanjing Medical University, Nanjing Women and Children's Healthcare Hospital, 123 Tianfei St. Qinhuai District, Nanjing, 210004, China.
Yun SunGenetic Medicine Center, Women's Hospital of Nanjing Medical University, Nanjing Women and Children's Healthcare Hospital, 123 Tianfei St. Qinhuai District, Nanjing, 210004, China.
Yanyun WangGenetic Medicine Center, Women's Hospital of Nanjing Medical University, Nanjing Women and Children's Healthcare Hospital, 123 Tianfei St. Qinhuai District, Nanjing, 210004, China.
Yahong LiGenetic Medicine Center, Women's Hospital of Nanjing Medical University, Nanjing Women and Children's Healthcare Hospital, 123 Tianfei St. Qinhuai District, Nanjing, 210004, China.
Zhilei ZhangGenetic Medicine Center, Women's Hospital of Nanjing Medical University, Nanjing Women and Children's Healthcare Hospital, 123 Tianfei St. Qinhuai District, Nanjing, 210004, China.
Dongyang HongGenetic Medicine Center, Women's Hospital of Nanjing Medical University, Nanjing Women and Children's Healthcare Hospital, 123 Tianfei St. Qinhuai District, Nanjing, 210004, China.
Peiying YangGenetic Medicine Center, Women's Hospital of Nanjing Medical University, Nanjing Women and Children's Healthcare Hospital, 123 Tianfei St. Qinhuai District, Nanjing, 210004, China.
Xiaowei LiangGenetic Medicine Center, Women's Hospital of Nanjing Medical University, Nanjing Women and Children's Healthcare Hospital, 123 Tianfei St. Qinhuai District, Nanjing, 210004, China.
Xin WangGenetic Medicine Center, Women's Hospital of Nanjing Medical University, Nanjing Women and Children's Healthcare Hospital, 123 Tianfei St. Qinhuai District, Nanjing, 210004, China. xinwang19911111@njmu.edu.cn.ORCID http://orcid.org/0000-0003-4531-2908
Bin YuDepartment of Medical Genetics, Changzhou Maternal and Child Health Care Hospital, Changzhou Medical Center of Nanjing Medical University, 16 Dingxiang St. Zhonglou District, Changzhou, 213000, China. binyu@njmu.edu.cn.

Funding

National Natural Science Foundation of China No. 32100680
6 · The paper itself

Abstract

backgroundWilson disease (WD) is an autosomal recessive disorder caused by variants in the ATP7B gene, leading to copper metabolism dysfunction and multi-organ damage. Early diagnosis is critical for improving clinical outcomes, but current screening methods have limitations. Metabolomics can reveal early metabolic disturbances in disease; however, the metabolic profile of newborns with WD remains unexplored. This study aimed to identify potential metabolic biomarkers for early WD detection through untargeted metabolomic analysis.

methodsDried blood spot (DBS) samples from six genetically confirmed WD positive newborns and 84 healthy controls were analyzed using liquid chromatography-mass spectrometry (LC-MS). Multivariate statistical analysis was employed to identify differentially abundant metabolites. Pathway enrichment analysis and receiver operating characteristic (ROC) curve evaluation were performed to assess diagnostic performance.

resultsA total of 29 significantly altered metabolites (21 upregulated, 8 downregulated) were identified in WD positive newborns, primarily associated with tyrosine metabolism. ROC analysis revealed 11 metabolites with an area under the curve (AUC) > 90%. Additionally, two pairs of isomers also demonstrated exhibited high diagnostic sensitivity and specificity and were closely linked to WD pathogenesis. In positive group, tyrosine metabolism pathway was most significantly affected, as evidenced by increased levels of 3,4-Dihydroxyphenylacetic acid and Homogentisic acid, alongside a decreased level of Gentisaldehyde.

conclusionWD positive newborns exhibit distinct metabolic reprogramming prior to copper accumulation, with tyrosine metabolism dysregulation as a potential early feature. The identified differential metabolites may serve as promising biomarkers for newborn WD screening, providing a foundation for metabolomics-based early diagnostic strategies.

Indexed as

BiomarkersHepatolenticular DegenerationHigh-Throughput Nucleotide SequencingMetabolomicsFemaleHumansInfant, NewbornLiquid Chromatography-Mass SpectrometryMaleROC CurveBiomarkersDifferential metabolitesLiver damageNeurological symptomsTyrosine metabolismWilson’s disease

Identifiers

PMID41454338
PMCPMC12853665

What Socratic holds

Textmetadata
LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.