ArticleAnnals of neurology2019
PDXK mutations cause polyneuropathy responsive to pyridoxal 5'-phosphate supplementation.
Article in Annals of neurology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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.
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Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 73 citations in OpenAlex.
- Pooled it
- 2nd NMD4C basic research summer school on promoting standardized protocols to advance translational research in neuromuscular disorders.Journal of neuromuscular diseases · 2026Article
- PDXK-Related Neuropathy: A Case With a Novel Splice-Altering Missense Variant and Literature Review.Molecular genetics & genomic medicine · 2026Review
- PDXK Mutation Causes a Late-Onset Pyridoxal 5'-Phosphate-Responsive Peripheral Neuropathy Preceded by Neonatal Seizures.Indian journal of pediatrics · 2026Article
- Do Glioma Cells Rewire Neural Circuits through Epigenetic Changes? DNA Methylation Analysis of Genes Involved in Neuron-Glioma Communication in the Human Frontal Cortex.Journal of molecular neuroscience : MN · 2025Article
- Potential Causal Relationships Between Circulating Micronutrient Levels and Multiple Neuroimmune Diseases: A Genetic Association Analysis.Brain and behavior · 2025Article
- Mendelian randomization study of micronutrients and development of CKD in a Korean population.Nutrition journal · 2025Article
- SLC25A38 is required for mitochondrial pyridoxal 5'-phosphate (PLP) accumulation.Nature communications · 2025Article
- Toxic Effects of Excess Vitamins A, B6, and Folic Acid on the Nervous System.Behavioural neurology · 2025Review
- Rare disease genomics and precision medicine.Genomics & informatics · 2024Review
- Natural product P57 induces hypothermia through targeting pyridoxal kinase.Nature communications · 2023Article
- Vitamin BScience advances · 2023Article
- Transcriptomic profiling of Parkinson's disease brains reveals disease stage specific gene expression changes.Acta neuropathologica · 2023Article
- Vitamin B6 regulates IL-33 homeostasis to alleviate type 2 inflammation.Cellular & molecular immunology · 2023Article
- Review
- The Rationale for Vitamin, Mineral, and Cofactor Treatment in the Precision Medical Care of Autism Spectrum Disorder.Journal of personalized medicine · 2023Review
- IGF1 deficiency integrates stunted growth and neurodegeneration in Down syndrome.Cell reports · 2022Article
- Care4Rare Canada: Outcomes from a decade of network science for rare disease gene discovery.American journal of human genetics · 2022Review
- Simplifying the B Complex: How Vitamins B6 and B9 Modulate One Carbon Metabolism in Cancer and Beyond.Metabolites · 2022Review
- B vitamin supply in plants and humans: the importance of vitamer homeostasis.The Plant journal : for cell and molecular biology · 2022Review
Corrections and comments
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Authors and funding
39 authors at 12 institutions in 9 countries.
Funding
Abstract
objectiveTo identify disease-causing variants in autosomal recessive axonal polyneuropathy with optic atrophy and provide targeted replacement therapy.
methodsWe performed genome-wide sequencing, homozygosity mapping, and segregation analysis for novel disease-causing gene discovery. We used circular dichroism to show secondary structure changes and isothermal titration calorimetry to investigate the impact of variants on adenosine triphosphate (ATP) binding. Pathogenicity was further supported by enzymatic assays and mass spectroscopy on recombinant protein, patient-derived fibroblasts, plasma, and erythrocytes. Response to supplementation was measured with clinical validated rating scales, electrophysiology, and biochemical quantification.
resultsWe identified biallelic mutations in PDXK in 5 individuals from 2 unrelated families with primary axonal polyneuropathy and optic atrophy. The natural history of this disorder suggests that untreated, affected individuals become wheelchair-bound and blind. We identified conformational rearrangement in the mutant enzyme around the ATP-binding pocket. Low PDXK ATP binding resulted in decreased erythrocyte PDXK activity and low pyridoxal 5'-phosphate (PLP) concentrations. We rescued the clinical and biochemical profile with PLP supplementation in 1 family, improvement in power, pain, and fatigue contributing to patients regaining their ability to walk independently during the first year of PLP normalization.
interpretationWe show that mutations in PDXK cause autosomal recessive axonal peripheral polyneuropathy leading to disease via reduced PDXK enzymatic activity and low PLP. We show that the biochemical profile can be rescued with PLP supplementation associated with clinical improvement. As B
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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.