Teaching Video NeuroImages: Atypical Abnormal Eye Movements in
            <i>PNPO</i>
            -Related Epilepsy

Pavitt, Sara; Karamian, Amanda G. Sandoval; Chattree, Gaurav; Klotz, Jenna; Beres, Shannon

doi:10.1212/wnl.0000000000010861

Cited by 2 publications

(2 citation statements)

References 2 publications

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“…Similar to PDE-ALDH7A1, PNPO deficiency is characterized by early onset, drug-resistant epileptic encephalopathy [87]. Since the disease gene discovery in 2005 [57], about 90 cases of PNPO deficiency have been reported in the medical literature with a phenotypic spectrum that extends from early postnatal lethality to milder forms with well-controlled seizures and normal neurodevelopmental outcome [88,[97][98][99]. Prematurity is observed in about 50% of the PNPO deficiency cases [88].…”

Section: Clinical Featuresmentioning

confidence: 99%

“…In utero onset of seizures have been suspected in some of the documented cases [87]. PNPO-deficient patients may also suffer from variable degrees of morphological brain defects, most commonly diffuse brain atrophy, and neurodevelopmental deficits [88] as well as systemic co-morbidities such as lactic acidosis, hypoglycaemia, coagulopathy, anemia and ocular and cardiac problems [6,37,86,98].…”

Section: Clinical Featuresmentioning

confidence: 99%

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Vitamin B6 and Related Inborn Errors of Metabolism

Al-Shekaili¹,

Leavitt²

2022

B-Complex Vitamins - Sources, Intakes and Novel Applications

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Vitamin B6 (vitB6) is a generic term that comprises six interconvertible pyridine compounds. These vitB6 compounds (also called vitamers) are pyridoxine (PN), pyridoxamine (PM), pyridoxal (PL) and their 5′-phosphorylated forms pyridoxine 5′-phosphate (PNP), pyridoxamine 5′-phosphate (PMP) and pyridoxal 5′-phosphate (PLP). VitB6 is an essential nutrient for all living organisms, but only microorganisms and plants can carry out de novo synthesis of this vitamin. Other organisms obtain vitB6 from dietary sources and interconvert its different forms according to their needs via a biochemical pathway known as the salvage pathway. PLP is the biologically active form of vitB6 which is important for maintaining the biochemical homeostasis of the body. In the human body, PLP serves as a cofactor for more than 140 enzymatic reactions, mainly associated with synthesis, degradation and interconversion of amino acids and neurotransmitter metabolism. PLP-dependent enzymes are also involved in various physiological processes, including biologically active amine biosynthesis, lipid metabolism, heme synthesis, nucleic acid synthesis, protein and polyamine synthesis and several other metabolic pathways. PLP is an important vitamer for normal brain function since it is required as a coenzyme for the synthesis of several neurotransmitters including D-serine, D-aspartate, L-glutamate, glycine, γ-aminobutyric acid (GABA), serotonin, epinephrine, norepinephrine, histamine and dopamine. Intracellular levels of PLP are tightly regulated and conditions that disrupt this homeostatic regulation can cause disease. In humans, genetic and dietary (intake of high doses of vitB6) conditions leading to increase in PLP levels is known to cause motor and sensory neuropathies. Deficiency of PLP in the cell is also implicated in several diseases, the most notable example of which are the vitB6-dependent epileptic encephalopathies. VitB6-dependent epileptic encephalopathies (B6EEs) are a clinically and genetically heterogeneous group of rare inherited metabolic disorders. These debilitating conditions are characterized by recurrent seizures in the prenatal, neonatal, or postnatal period, which are typically resistant to conventional anticonvulsant treatment but are well-controlled by the administration of PN or PLP. In addition to seizures, children affected with B6EEs may also suffer from developmental and/or intellectual disabilities, along with structural brain abnormalities. Five main types of B6EEs are known to date, these are: PN-dependent epilepsy due to ALDH7A1 (antiquitin) deficiency (PDE-ALDH7A1) (MIM: 266100), hyperprolinemia type 2 (MIM: 239500), PLP-dependent epilepsy due to PNPO deficiency (MIM: 610090), hypophosphatasia (MIM: 241500) and PLPBP deficiency (MIM: 617290). This chapter provides a review of vitB6 and its different vitamers, their absorption and metabolic pathways in the human body, the diverse physiological roles of vitB6, PLP homeostasis and its importance for human health. Finally, the chapter reviews the inherited neurological disorders affecting PLP homeostasis with a special focus on vitB6-dependent epileptic encephalopathies (B6EEs), their different subtypes, the pathophysiological mechanism underlying each type, clinical and biochemical features and current treatment strategies.

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Section: Clinical Featuresmentioning

confidence: 99%

Section: Clinical Featuresmentioning

confidence: 99%

Vitamin B6 and Related Inborn Errors of Metabolism

Al-Shekaili¹,

Leavitt²

2022

B-Complex Vitamins - Sources, Intakes and Novel Applications

View full text Add to dashboard Cite

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Epilepsy Phenotypes of Vitamin B6-Dependent Diseases: An Updated Systematic Review

et al. 2023

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Background: Vitamin B6-dependent epilepsies include treatable diseases responding to pyridoxine or pyridoxal-5Iphosphate (ALDH7A1 deficiency, PNPO deficiency, PLP binding protein deficiency, hyperprolinemia type II and hypophosphatasia and glycosylphosphatidylinositol anchor synthesis defects). Patients and methods: We conducted a systematic review of published pediatric cases with a confirmed molecular genetic diagnosis of vitamin B6-dependent epilepsy according to PRISMA guidelines. Data on demographic features, seizure semiology, EEG patterns, neuroimaging, treatment, and developmental outcomes were collected. Results: 497 published patients fulfilled the inclusion criteria. Seizure onset manifested at 59.8 ± 291.6 days (67.8% of cases in the first month of life). Clonic, tonic-clonic, and myoclonic seizures accounted for two-thirds of the cases, while epileptic spasms were observed in 7.6%. Burst-suppression/suppression-burst represented the most frequently reported specific EEG pattern (14.4%), mainly in PLPB, ALDH7A1, and PNPO deficiency. Pyridoxine was administered to 312 patients (18.5% intravenously, 76.9% orally, 4.6% not specified), and 180 also received antiseizure medications. Pyridoxine dosage ranged between 1 and 55 mg/kg/die. Complete seizure freedom was achieved in 160 patients, while a significant seizure reduction occurred in 38. PLP, lysine-restricted diet, and arginine supplementation were used in a small proportion of patients with variable efficacy. Global developmental delay was established in 30.5% of a few patients in whom neurocognitive tests were performed. Conclusions: Despite the wide variability, the most frequent hallmarks of the epilepsy phenotype in patients with vitamin B6-dependent seizures include generalized or focal motor seizure semiology and a burst suppression/suppression burst pattern in EEG.

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Teaching Video NeuroImages: Atypical Abnormal Eye Movements in PNPO -Related Epilepsy

Cited by 2 publications

References 2 publications

Vitamin B6 and Related Inborn Errors of Metabolism

Vitamin B6 and Related Inborn Errors of Metabolism

Epilepsy Phenotypes of Vitamin B6-Dependent Diseases: An Updated Systematic Review

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