Evidence map›Paper›PMID 39729892›Full record

ArticleMolecular genetics and metabolism2025

Feasibility of newborn screening for pyridoxine-dependent epilepsy.

Kristine Pauly, Michael Woontner, Jose E Abdenur, Bimal P Chaudhari, Rachel Gosselin, Kimberly A Kripps, Janet A Thomas, Michael F Wempe, Sidney M Gospe, Curtis R Coughlin

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In one paragraph

Article in Molecular genetics and metabolism, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
  4. Article
  5. LysineFrontiers in molecular neuroscience · 2025
    Review
  6. Article
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.

Kristine PaulySection of Clinical Genetics and Metabolism, Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Michael WoontnerSection of Clinical Genetics and Metabolism, Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Jose E AbdenurDivision of Metabolic Disorders, CHOC Children's Hospital, Orange, CA, USA.
Bimal P ChaudhariDepartment of Pediatrics, Division of Genetics and Genomic Medicine, Nationwide Children's Hospital, Columbus, OH, USA; Department of Pediatrics, Division of Neonatology, Nationwide Children's Hospital, Columbus, OH, USA; Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, OH, USA; Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, USA.
Rachel GosselinDepartment of Pediatrics, Division of Genetics and Genomic Medicine, Nationwide Children's Hospital, Columbus, OH, USA.
Kimberly A KrippsDepartment of Molecular and Medical Genetics, Oregon Health & Science University, Portland, OR, USA.
Janet A ThomasSection of Clinical Genetics and Metabolism, Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Michael F WempeSchool of Pharmacy, Department of Pharmaceutical Sciences, University of Colorado, Aurora, CO, USA; Univeristy of Colorado Cancer Center, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Sidney M GospeDepartments of Neurology and Pediatrics, University of Washington School of Medicine, Seattle, WA, USA; Seattle Children's Research Institute, Seattle, WA, USA; Department of Pediatrics, Duke University, Durham, NC, USA.
Curtis R CoughlinSection of Clinical Genetics and Metabolism, Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA. Electronic address: Curtis.Coughlin@cuanschutz.edu.

Funding

Newborn screening and treatment monitoring for patients with pyridoxine-dependent epilepsyR21HD104952 · NICHD · UNIVERSITY OF COLORADO DENVER · PI COUGHLIN, CURTIS R · 2022 to 2023
$428k
NICHD NIH HHS R21 HD104952
6 · The paper itself

Abstract

backgroundPyridoxine-dependent epilepsy (PDE-ALDH7A1) is a developmental epileptic encephalopathy historically characterized by seizures that are resistant to antiseizure medications. Treatment with pyridoxine and lysine reduction therapies are associated with seizure control and improved developmental outcomes. In rare circumstances, patients have died prior to diagnosis and treatment with pyridoxine, and many patients are diagnosed after six months of age when lysine reduction therapies have limited efficacy. Recently two new metabolites were identified (2S,6S-/2S,6R-oxopropylpiperidine-2-carboxylic acid, 2-OPP and 6-oxo-pipecolate, 6-oxo-pip), and we evaluated these metabolites as potential newborn screening biomarkers.

methodsWe recruited participants with a confirmed diagnosis of PDE-ALDH7A1 and retrieved their residual dried blood spots from state-sponsored newborn screening programs. We evaluated the dried blood spots for 2-OPP using commercially available newborn screening kits and equipment, and developed a second-tier test for 6-oxo-pip using LC-MS/MS.

resultsWe received eight residual dried blood spots collected before the onset of seizures and the diagnosis of PDE-ALDH7A1. In our newborn screening experiments, 2-OPP was elevated in 7 of 8 samples from affected participants with a mean of 3.08 μmol/L (95 % CI 2.17-3.99) compared to a mean of 0.09 μmol/L (95 % CI 0.09-0.10) in controls (p < 0.001). Second tier testing demonstrated elevated 6-oxo-pip in all samples from affected participants with a mean of 5.66 μmol/L (95 % CI 1.51-9.81) and was undetectable in controls (p < 0.001).

conclusionPatients with PDE-ALDH7A1 can be identified using neonatal dried blood spots prior to the onset of symptoms. The use of commercially available newborn screening approaches demonstrates the feasibility of newborn screening for this treatable condition.

Indexed as

Aldehyde DehydrogenaseEpilepsyNeonatal ScreeningPyridoxineBiomarkersDried Blood Spot TestingFeasibility StudiesFemaleHumansInfant, NewbornMalePipecolic AcidsTandem Mass SpectrometryAldehyde DehydrogenaseALDH7A1 protein, humanBiomarkerspipecolic acidPipecolic AcidsPyridoxine6-oxo-pipecolateALDH7A1Newborn screeningPDE-ALDH7A1Pyridoxine-dependent epilepsy

Identifiers

PMID39729892
PMCPMC12396694

What OpenQuestion holds

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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 OpenQuestion graph.