Evidence map›Paper›PMID 42348032›Full record

ReviewMetabolomics : Official journal of the Metabolomic Society2026

Next-generation newborn screening: feasibility of combined genetic and biochemical testing for 95 treatable inherited metabolic disorders.

Abigail Veldman, C Edel Arar, M B Gea Kiewiet, Els Voorhoeve, Martijn E T Dollé, Monique de Sain-van der Velden, Rose E Maase, Francjan J van Spronsen, Birgit Sikkema-Raddatz, M Rebecca Heiner-Fokkema

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PubMed Full text at PMC Publisher
In one paragraph

Review in Metabolomics : Official journal of the Metabolomic Society, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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.

Abigail VeldmanDivision of Metabolic Diseases, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
C Edel ArarDepartment of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
M B Gea KiewietDepartment of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Els VoorhoeveCentre for Health Protection, National Institute for Public Health and the Environment, Bilthoven, The Netherlands.
Martijn E T DolléCentre for Health Protection, National Institute for Public Health and the Environment, Bilthoven, The Netherlands.
Monique de Sain-van der VeldenSection Metabolic Diagnostics, Department of Genetics, University Medical Centre Utrecht, Utrecht, The Netherlands.
Rose E MaaseCentre for Health Protection, National Institute for Public Health and the Environment, Bilthoven, The Netherlands.
Francjan J van SpronsenDivision of Metabolic Diseases, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Birgit Sikkema-RaddatzDepartment of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
M Rebecca Heiner-FokkemaLaboratory of Metabolic Diseases, Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. m.r.heiner@umcg.nl.

Funding

Rijksinstituut voor Volksgezondheid en Milieu S/132015ZonMw No. 50-54300-98-506
6 · The paper itself

Abstract

introductionNext-generation sequencing (NGS) is gaining attention in newborn screening (NBS) for its ability to detect treatable genetic disorders, especially those without a biochemical footprint. However, NGS-NBS requires interpreting variants without phenotype information or family trio analysis. Biochemical tests, preferably in dried blood spots (DBS), are therefore useful to confirm the pathogenicity of variants identified by NGS-NBS and increase its specificity and sensitivity.

objectivesWe aimed to explore the potential of combined genetic-biochemical testing for 95 treatable Inherited Metabolic Disorders (IMD) considered eligible for NGS-NBS (100 genes) previously identified by our research group.

methodsWe reviewed the Collaborative Laboratory Integrated Reports (CLIR) and carried out systematic literature reviews in PubMed and Embase to identify biochemical tests for 95 IMD. Biochemical tests conducted on DBS were differentiated from tests that require referral.

resultsWe identified DBS-biochemical tests for 72 of the 95 IMD (77/100 genes). DBS-based biochemical tests for 55 IMD (60 genes) are already implemented in NBS. For the other 23 IMD, biochemical tests in non-DBS specimens are reported, although some are less sensitive when measured at neonatal age in presymptomatic infants.

conclusionWe present a comprehensive overview of current biochemical tests for 95 IMD. These tests can be used to confirm inconclusive NGS-NBS results, and combined genetic-biochemical testing is expected to improve both the negative and positive predictive values of NBS programs.

Indexed as

Genetic TestingHigh-Throughput Nucleotide SequencingMetabolic DiseasesMetabolism, Inborn ErrorsNeonatal ScreeningDried Blood Spot TestingHumansInfant, NewbornBiochemical testingBiomarkersDNA-based screeningDried blood spotGenomic screeningInherited metabolic diseasesNewborn screeningNext-generation sequencing

Identifiers

PMID42348032
PMCPMC13303320

What Socratic holds

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LicenceCC BY
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Registered trials

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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.