ArticleJournal of inherited metabolic disease2018
Next-generation metabolic screening: targeted and untargeted metabolomics for the diagnosis of inborn errors of metabolism in individual patients.
Article in Journal of inherited metabolic disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 108 papers, 2 of them syntheses that pooled 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.
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.
Who cites it
108 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Metabolomic profiling in phenylketonuria: a systematic review of human studies.Metabolomics : Official journal of the Metabolomic Society · 2026Pooled it
- Catching the Culprit: How Chorea May Signal an Inborn Error of Metabolism.Tremor and other hyperkinetic movements (New York, N.Y.) · 2023Pooled it
- Pipettes and Pipelines: The Weapons of Omics Sciences for a New Age of Clinical Studies.Current issues in molecular biology · 2026Review
- Historical Perspectives, Classification and Diagnostic Approaches of Inborn Errors of Metabolism: A Systematic Review and Meta-Analysis.Metabolites · 2026Review
- A Novel Multimodal LC-MS/MS Panel for the Comprehensive Diagnosis of Neurometabolic Disorders in CSF.Journal of inherited metabolic disease · 2026Article
- Article
- Untargeted Metabolomics for Diagnosis, Monitoring, and Understanding the Pathophysiology of Inherited Metabolic Disorders.Journal of inherited metabolic disease · 2026Review
- Untargeted Metabolomics Reveals Metabolic Reprogramming Linked to HCC Risk in Late Diagnosed Tyrosinemia Type 1.Metabolites · 2025Article
- Targeting AASS alleviates neurotoxicity and improves mitochondrial function in astrocyte models for pyridoxine-dependent epilepsy.Molecular therapy. Nucleic acids · 2025Article
- Application of high-resolution mass spectrometry profiling towards the diagnosis and acute management of maple syrup urine disease.Molecular genetics and metabolism reports · 2025Article
- Endosomal Mechanisms in Heart Failure Pathophysiology.Current heart failure reports · 2025Review
- Trial Readiness: Understanding the Natural History of Rare Diseases.Journal of inherited metabolic disease · 2025Review
- Identification of an extraction protocol from dried blood spots for untargeted metabolomics: application to phenylketonuria.Metabolomics : Official journal of the Metabolomic Society · 2025Article
- Potential Biomarkers of Carbohydrate Metabolism Disorders: A Pilot Study.Bulletin of experimental biology and medicine · 2025Article
- A diagnostic algorithm for inherited metabolic disorders using untargeted metabolomics.Metabolomics : Official journal of the Metabolomic Society · 2025Article
- Beyond Targeted Newborn Screening: A Nontargeted Metabolomics Workflow to Investigate Birthweight-Metabolome Correlations.Analytical chemistry · 2025Article
- Article
- X-Linked Autism Type 9 Caused by a Hemizygote Pathogenic Variant in theInternational medical case reports journal · 2025Article
- Global Metabolomics Using LC-MS for Clinical Applications.Methods in molecular biology (Clifton, N.J.) · 2025Article
- New treatment for pyridoxine-dependent epilepsy due to ALDH7A1 deficiency: first proof-of-principle of upstream enzyme inhibition in the mouse.Brain communications · 2025Article
48 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The implementation of whole-exome sequencing in clinical diagnostics has generated a need for functional evaluation of genetic variants. In the field of inborn errors of metabolism (IEM), a diverse spectrum of targeted biochemical assays is employed to analyze a limited amount of metabolites. We now present a single-platform, high-resolution liquid chromatography quadrupole time of flight (LC-QTOF) method that can be applied for holistic metabolic profiling in plasma of individual IEM-suspected patients. This method, which we termed "next-generation metabolic screening" (NGMS), can detect >10,000 features in each sample. In the NGMS workflow, features identified in patient and control samples are aligned using the "various forms of chromatography mass spectrometry (XCMS)" software package. Subsequently, all features are annotated using the Human Metabolome Database, and statistical testing is performed to identify significantly perturbed metabolite concentrations in a patient sample compared with controls. We propose three main modalities to analyze complex, untargeted metabolomics data. First, a targeted evaluation can be done based on identified genetic variants of uncertain significance in metabolic pathways. Second, we developed a panel of IEM-related metabolites to filter untargeted metabolomics data. Based on this IEM-panel approach, we provided the correct diagnosis for 42 of 46 IEMs. As a last modality, metabolomics data can be analyzed in an untargeted setting, which we term "open the metabolome" analysis. This approach identifies potential novel biomarkers in known IEMs and leads to identification of biomarkers for as yet unknown IEMs. We are convinced that NGMS is the way forward in laboratory diagnostics of IEMs.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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 OpenQuestion graph.