ArticleJournal of inherited metabolic disease2022
Cerebrospinal fluid amino acids glycine, serine, and threonine in nonketotic hyperglycinemia.
Article in Journal of inherited metabolic disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 26 citations in OpenAlex.
- Plasma serine and glycine in relation to clinical outcomes following neoadjuvant radiotherapy for rectal cancer.Clinical and translational radiation oncology · 2026Article
- Glutamatergic Neurotransmission Disruption as a Pathomechanism of Brain Damage in Disorders of Amino Acid and Organic Acid Metabolism: Insights from Animal and Cellular Studies.Neurochemical research · 2026Review
- 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
- d-amino acids: new functional insights.The FEBS journal · 2025Review
- Nanomedicines Targeting Metabolic Pathways in the Tumor Microenvironment: Future Perspectives and the Role of AI.Metabolites · 2025Review
- Deep postnatal phenotyping of a new mouse model of nonketotic hyperglycinemia.Journal of inherited metabolic disease · 2024Article
- GC/MS-Based Metabolomic Analysis of A549 Cells Exposed to Emerging Organophosphate Flame Retardants.Toxics · 2024Article
- The behavioral phenotype of children and adolescents with attenuated non-ketotic hyperglycinemia, intermediate to good subtype.Orphanet journal of rare diseases · 2024Article
- Metabolic Rewiring and Altered Glial Differentiation in an iPSC-Derived Astrocyte Model Derived from a Nonketotic Hyperglycinemia Patient.International journal of molecular sciences · 2024Article
- Therapeutic potential of N-methyl-D-aspartate receptor modulators in psychiatry.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Review
- Traffic Density Exposure, Oxidative Stress Biomarkers and Plasma Metabolomics in a Population-Based Sample: The Hortega Study.Antioxidants (Basel, Switzerland) · 2023Article
- Article
- Ketogenic diet as a glycine lowering therapy in nonketotic hyperglycinemia and impact on brain glycine levels.Orphanet journal of rare diseases · 2022Article
- Cerebrospinal fluid amino acids glycine, serine, and threonine in nonketotic hyperglycinemia.Journal of inherited metabolic disease · 2022Article
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Authors and funding
11 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nonketotic hyperglycinemia (NKH) is caused by deficient glycine cleavage enzyme activity and characterized by elevated brain glycine. Metabolism of glycine is connected enzymatically to serine through serine hydroxymethyltransferase and shares transporters with serine and threonine. We aimed to evaluate changes in serine and threonine in NKH patients, and relate this to clinical outcome severity. Age-related reference values were developed for cerebrospinal fluid (CSF) serine and threonine from 274 controls, and in a cross-sectional study compared to 61 genetically proven NKH patients, categorized according to outcome. CSF d-serine and l-serine levels were stereoselectively determined in seven NKH patients and compared to 29 age-matched controls. In addition to elevated CSF glycine, NKH patients had significantly decreased levels of CSF serine and increased levels of CSF threonine, even after age-adjustment. The CSF serine/threonine ratio discriminated between NKH patients and controls. The CSF glycine/serine aided in discrimination between severe and attenuated neonates with NKH. Over all ages, the CSF glycine, serine and threonine had moderate to fair correlation with outcome classes. After age-adjustment, only the CSF glycine level provided good discrimination between outcome classes. In untreated patients, d-serine was more reduced than l-serine, with a decreased d/l-serine ratio, indicating a specific impact on d-serine metabolism. We conclude that in NKH the elevation of glycine is accompanied by changes in l-serine, d-serine and threonine, likely reflecting a perturbation of the serine shuttle and metabolism, and of one-carbon metabolism. This provides additional guidance on diagnosis and prognosis, and opens new therapeutic avenues to be explored.
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