Evidence map›Paper›PMID 41603187›Full record

ArticleJournal of inherited metabolic disease2026

A Nonketotic Hyperglycinemia Mouse Shows Wide-Ranging Biochemical Consequences of Elevated Glycine, Reduced Folate One-Carbon Charging, and Serine Deficiency.

Michael A Swanson, Hua Jiang, Lakshmi Divya Kolora, Rachel Molino, Richard Reisdorph, Cole R Michel, Katrina A Doenges, Kit-Yi Leung, Xiangping Lin, Frank Wong and 15 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of inherited metabolic disease, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

25 authors.

Michael A SwansonDepartment of Pediatrics, Section of Clinical Genetics and Metabolism, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Hua JiangDepartment of Pediatrics, Section of Clinical Genetics and Metabolism, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Lakshmi Divya KoloraDepartment of Pediatrics, Section of Clinical Genetics and Metabolism, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Rachel MolinoDepartment of Pediatrics, Section of Clinical Genetics and Metabolism, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Richard ReisdorphDepartment of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Cole R MichelDepartment of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Katrina A DoengesDepartment of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Kit-Yi LeungDevelopmental Biology and Cancer Department, UCL Great Ormond Street Institute of Child Health, University College London, London, UK.
Xiangping LinDepartment of Genetics, Stanford School of Medicine, Stanford University, Stanford, California, USA.
Frank WongDepartment of Genetics, Stanford School of Medicine, Stanford University, Stanford, California, USA.
Samual LancasterDepartment of Genetics, Stanford School of Medicine, Stanford University, Stanford, California, USA.
Basil MichaelDepartment of Genetics, Stanford School of Medicine, Stanford University, Stanford, California, USA.
Michael SnyderDepartment of Genetics, Stanford School of Medicine, Stanford University, Stanford, California, USA.
Daniella H HockDepartment of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Victoria, Australia.
David A StroudDepartment of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Victoria, Australia.
Tim WoodDepartment of Pediatrics, Section of Clinical Genetics and Metabolism, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.ORCID https://orcid.org/0000-0003-0831-0188
Robert BinardDepartment of Pathology and Laboratory Medicine, Children's Hospital Colorado, Aurora, Colorado, USA.
Laura Anderson-LehmanDepartment of Pathology and Laboratory Medicine, Children's Hospital Colorado, Aurora, Colorado, USA.
Uwe ChristiansDepartment of Anesthesiology, iC42 Clinical Research and Development, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Erland ArningInstitute of Metabolic Disease, Baylor Scott and White Research Institute, Dallas, Texas, USA.
Marisa W FriederichDepartment of Pediatrics, Section of Clinical Genetics and Metabolism, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Roxanne A Van HoveDepartment of Pediatrics, Section of Clinical Genetics and Metabolism, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Kenneth N MacLeanDepartment of Pediatrics, Section of Clinical Genetics and Metabolism, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Nicholas D E GreeneDevelopmental Biology and Cancer Department, UCL Great Ormond Street Institute of Child Health, University College London, London, UK.
Johan L K Van HoveDepartment of Pediatrics, Section of Clinical Genetics and Metabolism, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.ORCID https://orcid.org/0000-0003-2850-3294

Funding

Barnett FamilyBrodyn's FriendsDickens Family FoundationJoseph's GoalLes Petits BourdonsLucas John FoundationMadi's Mission NKH FundMaud & Vic FoundationMedical Research Council W00500XNational Health and Medical Research Council 1140906National Health and Medical Research Council 2009732National Health and Medical Research Council 2016030NIH HHS S10 OD028538-01A1NKH CrusadersNora Jane Almany FoundationUniversity of Colorado FoundationWilliam R Hummel Research Fund
6 · The paper itself

Abstract

Nonketotic hyperglycinemia is a severe neonatal epileptic encephalopathy caused by deficient glycine cleavage enzyme activity, for which currently no effective treatment exists. Incomplete understanding of brain biochemistry represents a major knowledge gap to develop new treatments. We examined the biochemistry in blood, liver, cortex, hippocampus, and cerebellum of a mouse model homozygous for the Gldc variant p.Ala394Val. Glycine was increased in all compartments and caused increased brain neurotoxic metabolites guanidinoacetate and methylglyoxal, and also N-acetylglycine and cystathionine. The glycine extruding transporter Slc6a20 was increased. There was reduced one-carbon folate charging with secondarily reduced methionine in the cortex, and reduced alternative one-carbon donors L-serine and formate. Serine deficiency was associated with reduced amounts of sphingosine, sphingomyelin, and ceramide species important for myelination, but not phosphatidylserines. There was a region-specific deficiency of D-serine in the cortex and hippocampus. This difference, also present in humans, was strain- and age-related, most evident in young J129X1/SvJ mice, reflecting symptomatology. There was no evidence of oxidative stress or a bioenergetic defect. The biochemistry of the nonketotic hyperglycinemia mouse model can be traced to three components: increased glycine, reduced folate one-carbon charging, and decreased L- and D-serine. These changes will need to be addressed in new therapeutic approaches.

Indexed as

Folic AcidGlycineHyperglycinemia, NonketoticSerineAnimalsBrainDisease Models, AnimalGlycine Dehydrogenase (Decarboxylating)HippocampusHumansLiverMaleMiceFolic AcidGlycineGlycine Dehydrogenase (Decarboxylating)SerineD‐serineglycinelipidomicsL‐serinemetabolomicsmethyl‐tetrahydrofolatenonketotic hyperglycinemiaproteomics

Identifiers

PMID41603187
PMCPMC12848846

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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 OpenQuestion graph.