ArticleThe Journal of clinical investigation2020
Impaired folate 1-carbon metabolism causes formate-preventable hydrocephalus in glycine decarboxylase-deficient mice.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
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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.
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Who cites it
16 citing papers in PubMed, 26 citations in OpenAlex.
- Variants in glycine decarboxylase activate catabolic mechanisms of mitochondrial energy metabolism in the brain.The Journal of biological chemistry · 2026Article
- A Nonketotic Hyperglycinemia Mouse Shows Wide-Ranging Biochemical Consequences of Elevated Glycine, Reduced Folate One-Carbon Charging, and Serine Deficiency.Journal of inherited metabolic disease · 2026Article
- Surface enhanced Raman spectroscopy and machine learning as an accurate and rapid diagnostic tool for hydrocephalus.Scientific reports · 2025Article
- Deep postnatal phenotyping of a new mouse model of nonketotic hyperglycinemia.Journal of inherited metabolic disease · 2024Article
- (Zebra)fishing for nephrogenesis genes.Tissue barriers · 2024Review
- Metabolic Rewiring and Altered Glial Differentiation in an iPSC-Derived Astrocyte Model Derived from a Nonketotic Hyperglycinemia Patient.International journal of molecular sciences · 2024Article
- Article
- Mitochondrial FAD shortage in SLC25A32 deficiency affects folate-mediated one-carbon metabolism.Cellular and molecular life sciences : CMLS · 2022Article
- Impaired Folate-Mediated One-Carbon Metabolism in Type 2 Diabetes, Late-Onset Alzheimer's Disease and Long COVID.Medicina (Kaunas, Lithuania) · 2021Review
- Review
- Hormonal regulation of glycine decarboxylase and its relationship to oxidative stress.Physiological reports · 2021Article
- Brain Barriers and brain fluids research in 2020 and the fluids and barriers of the CNS thematic series on advances in in vitro modeling of the blood-brain barrier and neurovascular unit.Fluids and barriers of the CNS · 2021Article
- Article
- Glycine Cleavage System H Protein Is Essential for Embryonic Viability, Implying Additional Function Beyond the Glycine Cleavage System.Frontiers in genetics · 2021Article
- Regulation of glycine metabolism by the glycine cleavage system and conjugation pathway in mouse models of non-ketotic hyperglycinemia.Journal of inherited metabolic disease · 2020Article
- Mitochondrial Metabolism in Astrocytes Regulates Brain Bioenergetics, Neurotransmission and Redox Balance.Frontiers in neuroscience · 2020Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Ventriculomegaly and hydrocephalus are associated with loss of function of glycine decarboxylase (Gldc) in mice and in humans suffering from non-ketotic hyperglycinemia (NKH), a neurometabolic disorder characterized by accumulation of excess glycine. Here, we showed that ventriculomegaly in Gldc-deficient mice is preceded by stenosis of the Sylvian aqueduct and malformation or absence of the subcommissural organ and pineal gland. Gldc functions in the glycine cleavage system, a mitochondrial component of folate metabolism, whose malfunction results in accumulation of glycine and diminished supply of glycine-derived 1-carbon units to the folate cycle. We showed that inadequate 1-carbon supply, as opposed to excess glycine, is the cause of hydrocephalus associated with loss of function of the glycine cleavage system. Maternal supplementation with formate prevented both ventriculomegaly, as assessed at prenatal stages, and postnatal development of hydrocephalus in Gldc-deficient mice. Furthermore, ventriculomegaly was rescued by genetic ablation of 5,10-methylene tetrahydrofolate reductase (Mthfr), which results in retention of 1-carbon groups in the folate cycle at the expense of transfer to the methylation cycle. In conclusion, a defect in folate metabolism can lead to prenatal aqueduct stenosis and resultant hydrocephalus. These defects are preventable by maternal supplementation with formate, which acts as a 1-carbon donor.
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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.