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Last update 23 Jan 2025

Pyridoxine-Dependent Epilepsy

Last update 23 Jan 2025

Basic Info

Synonyms

AASA DEHYDROGENASE DEFICIENCY, Aasa Dehydrogenase Deficiency, Antiquitin deficiency

+ [20]

Introduction

A rare neurometabolic disease characterized by recurrent intractable seizures in the prenatal, neonatal and postnatal period that are resistant to anti-epileptic drugs (AEDs) but that are responsive to pharmacological dosages of pyridoxine (vitamin B6).

Clinical Trials associated with Pyridoxine-Dependent Epilepsy

NCT06054347

/ RecruitingNot ApplicableIIT

Standardized Evaluation of Long-term Neurocognitive Development of Children From Age 3 With Pyridoxine Dependent Epilepsy by Antiquitine Deficiency

This study aims to evaluate with the VINELAND II scale the long-term neurocognitive development of children above age 3 years with pyridoxine dependent epilepsy related to antiquitine deficiency.

Start Date29 Dec 2023

Sponsor / Collaborator

Centre Hospitalier Universitaire d'Angers

NCT05687474

/ RecruitingNot ApplicableIIT

Universal Genomic Newborn Screening in the Wallonia-Brussels Federation: Baby Detect

Newborn screening (NBS) is a global initiative of systematic testing at birth to identify babies with pre-defined severe but treatable conditions. With a simple blood test, rare genetic conditions can be easily detected, and the early start of transformative treatment will help avoid severe disabilities and increase the quality of life.
Baby Detect Project is an innovative NBS program using a panel of target sequencing that aims to identify 126 treatable severe early onset genetic diseases at birth caused by 361 genes. The list of diseases has been established in close collaboration with the Paediatricians of the University Hospital in Liege. The investigators use dedicated dried blood spots collected between the first day and 28 days of life of babies, after a consent sign by parents.

Start Date01 Sep 2022

Sponsor / Collaborator

Centre Hospitalier Universitaire de Liege

[+5]

ChiCTR2100054170

/ RecruitingEarly Phase 1IIT

Relevant clinical diagnosis process and special dietary therapy establishment in pyridoxine-dependent epilepsy

Start Date30 Dec 2021

Sponsor / Collaborator

Peking University First Hospital

100 Clinical Results associated with Pyridoxine-Dependent Epilepsy

100 Translational Medicine associated with Pyridoxine-Dependent Epilepsy

0 Patents (Medical) associated with Pyridoxine-Dependent Epilepsy

789

Literatures (Medical) associated with Pyridoxine-Dependent Epilepsy

01 Feb 2025·Clinica Chimica Acta

Determination of new biomarkers for diagnosis of pyridoxine dependent epilepsy in human plasma and urine by liquid chromatography-mass spectrometry

Article

Author: Damiano, Roberta ; Guerrini, Renzo ; Procopio, Elena ; Gasperini, Serena ; Della Bona, Maria ; Bettiol, Alessandra ; la Marca, Giancarlo

BACKGROUNDPyridoxine-dependent epilepsy (PDE) is a rare inborn error of lysine metabolism. To date, diagnosis of PDE relies on the quantification of α-AminoAdipic SemiAldehyde (α- AASA), Piperideine-6-Carboxylate (P6C) and Pipecolic acid (PA) in urine or plasma from patients with overt symptoms. However, these biomarkers are not specific, and their biochemical analysis is challenged by their instability and technical limitations. We set-up and validated a method for the quantification of two new biomarkers of PDE (2S,6S- and 2S,6R-oxopropylpiperidine-2-carboxylic acid, 2-OPP, and 6-oxopiperidine2-carboxylic acid, 6-oxoPIP) on human urine and plasma by LC-MS/MS, to overcome the diagnostic and technical challenges of old biomarkers.METHODSWe analysed urine and plasma samples by LC-MS/MS, and validated the method in both biological matrices.RESULTSWe performed the biomarkers extraction from a 10 µL aliquot of urine or plasma in around 15 min using water 100 % for urine, and a solution of water/methanol 50 % for plasma, respectively. The analytical method was validated and gave good linearity (r² > 0.999) in the range 0-15 µmol/L for 2-OPP and 0-25 µmol/L for 6-oxoPIP. In both matrices, the biomarkers were stable at different storage temperatures tested.CONCLUSIONSWe set-up and validated a reliable method and confirmed its clinical applicability on real samples from PDE patients. This method could be used as routine test for the diagnosis and monitoring of PDE.

01 Jan 2025·Molecular Genetics and Metabolism

Feasibility of newborn screening for pyridoxine-dependent epilepsy

Article

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

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.

05 Dec 2024·Microbiology Spectrum

Purine limitation prevents the exogenous pyridoxal 5′-phosphate accumulation of Salmonella enterica yggS mutants

Article

Author: Downs, Diana M. ; Ezekiel, Kailey S.

ABSTRACT YggS belongs to the highly conserved pyridoxal 5′-phosphate (PLP) binding protein family (COG0325) that is found in all domains of life. Though no precise biochemical activity or molecular mechanism has been determined for this protein, an involvement in vitamin B 6 homeostasis has been demonstrated in multiple organisms. In Salmonella enterica , loss of YggS results in altered B 6 vitamer pools, including an accumulation of PLP in the growth medium. Transposon mutagenesis identified an insertion upstream of purC (encoding 5′-phosphoribosyl-5-aminoimidazole-4- N -succinocarboxamide synthetase, EC 6.3.2.6) that eliminated accumulation of PLP in the spent medium. Genetic characterization of the insertion showed the causative effect was reduced expression of purC , which limited purine biosynthesis. Data herein shows that purine limitation decreased the exogenous accumulation of B 6 vitamers of a yggS mutant but did not suppress other yggS mutant phenotypes. Neither limitation for ATP, regulation by PurR, or decreased growth rate, all of which are direct consequences of purine limitation, prevented exogenous B 6 vitamer accumulation of a yggS mutant. This work establishes a relationship between the status of purine biosynthesis and the impact of a yggS mutation. It lays the foundation for continued efforts to identify the physiological role of YggS and its homologs. IMPORTANCE Pyridoxal 5′-phosphate is the active form of vitamin B 6 and is an essential cofactor in all domains of life. PLP can be synthesized de novo or salvaged from the environment from one of the six B 6 vitamers. B 6 vitamer levels appear to be tightly regulated, and alterations in their levels can have deleterious effects, most notably being the development of B6-dependent epilepsy in humans. YggS homologs are broadly conserved across multiple organisms and considered to be involved in maintaining B 6 homeostasis, though no specific mechanism has been defined. The current study showed that the exogenous accumulation of PLP caused by a lack of YggS can be prevented by purine limitation. The demonstration that purine limitation impacts exogenous PLP accumulation separates one consequence of a yggS mutation for further study and contributes to continuing efforts to define the biochemical and physiological roles of the COG0325 family of proteins.

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Pyridoxine-Dependent Epilepsy

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