Pyridoxine Dependency: Report of a Case of Intractable Convulsions in an Infant Controlled by Pyridoxine

Hunt, Andrew D.; Stokes, Joseph; McCrory, Wallace W.; Stroud, H. H.

doi:10.1542/peds.13.2.140

Cited by 371 publications

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“…Vitamin B6–dependent epilepsy is a heterogeneous group of disorders characterized by early onset seizures which respond to pyridoxine or pyridoxal-5′-phosphate (PLP) due to decreased availability of the active cofactor PLP ( Hunt et al, 1954 ; Mills et al, 2005 ; Mills et al, 2006 ; Darin et al, 2016 ). Pyridoxine-dependent epilepsy (PDE, OMIM: 266100) or ALDH7A1 deficiency (traditionally) and pyridox(am)ine-5′-phosphate oxidase ( PNPO ) deficiency (OMIM: 610090) are the most prevalent type ( Stockler et al, 2011 ).…”

Section: Introductionmentioning

confidence: 99%

A Rare Presentation Characterized by Epileptic Spasms in ALDH7A1, Pyridox(am)ine-5′-Phosphate Oxidase, and PLPBP Deficiency

et al. 2022

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Objective: To analyze the clinical feature, treatment, and prognosis of epileptic spasms (ES) in vitamin B6–dependent epilepsy, including patients with pyridoxine-dependent epilepsy (PDE) caused by ALDH7A1 mutation, pyridox(am)ine-5′-phosphate oxidase (PNPO) deficiency, and PLPBP deficiency.Methods: We analyzed data from a cohort of 54 cases with PDE, 13 cases with PNPO deficiency, and 2 cases with PLPBP deficiency and looked for the presentation of ES among them.Results: A total of 11 patients with the seizure presentation of ES have been collected. Among them, four patients carried mutations in ALDH7A1, six carried mutations in PNPO, and the remaining one carried mutation in PLPBP. The analysis of this cohort identified nine cases presenting as infantile spasms distributed in the three diseases and two cases presenting as Ohtahara syndrome diagnosed with PDE and PNPO deficiency, respectively. In the PDE and PLPBP deficiency groups, seizures were controlled by pyridoxine monotherapy, and the remaining one had refractory seizures due to secondary brain atrophy. In the groups with PNPO deficiency, one patient showed seizure-free when treated by PLP combined with valproic acid, three still had infrequent seizures treated by PLP monotherapy or pyridoxine or PLP combined with other antiseizure medications, and two died. In two cases presenting as Ohtahara syndrome, after regular treatment, one showed seizure-free, the others showed a marked decrease in seizure frequency, and they both showed an improvement in EEG.Significance: ES might be a common form of seizures in PNPO deficiency, and EEG presented as hypsarrhythmia or a burst suppression pattern. It is difficult for pyridoxine to control frequent seizures caused by secondary brain injury. In our PNPO deficiency cohort, patients with infantile spasms did not respond better to PLP than pyridoxine. Timely and correct treatment could prevent the transformation of the child’s disease from Ohtahara syndrome and infantile spasms to subsequent epileptic encephalopathy or refractory epilepsy.

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Section: Introductionmentioning

confidence: 99%

A Rare Presentation Characterized by Epileptic Spasms in ALDH7A1, Pyridox(am)ine-5′-Phosphate Oxidase, and PLPBP Deficiency

et al. 2022

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“…According to the report, partial patients diagnosed with IS responded to high-dose vitamin B6, and a series of similar cases have been reported ( 2 – 9 ). Following the availability of genetic studies, vitamin B6-dependent epilepsy, a heterogeneous group of disorders causing seizures that can be controlled or significantly improved by high doses of vitamin B6, including pyridoxine-dependent epilepsy (PDE), pyridox(am)ine-5′-phosphate oxidase (PNPO) deficiency and PLPBP deficiency, was formally diagnosed and treated ( 10 – 13 ). However, partial patients with IS do not have the genetic mutation characteristic of vitamin B6-dependent epilepsy, and they also dramatically respond to high-dose vitamin B6 therapy.…”

Section: Introductionmentioning

confidence: 99%

The Clinical Features and Long-Term Follow-Up of Vitamin B6-Responsive Infantile Spasms in a Chinese Cohort

et al. 2022

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ObjectiveTo analyze the clinical features, treatment, and prognosis of patients with vitamin B6-responsive infantile spasms (IS).MethodsThe clinical features, genetics, and follow-up data of 30 patients were collected and analyzed.ResultsThe age of epileptic spasms (ES) onset was from 3 months to 12 months. They all received high doses of vitamin B6 at different times after the onset of ES, ranging from 1 day to 5 months. ES were controlled within 11 days in 93% (28/30) patients, and as late as 1 month and 2 months in the other two patients. In the course of treatment, 28 patients were seizure-free all the time, and seizures of other two patients recurred due to withdrawal of vitamin B6. The available follow-up EEG results of 28 patients were normal in 26 cases, and 81% (21/26) had suppressed epileptic discharges within 6 months. Of the 26 cases with normal follow up EEG, 4 had developmental delay and 22 had normal development. The time for EEG to return to normal in 22 patients with normal development ranged from 14 days to 2 years (mean = 111.5 days; median = 52.5 days). The time for EEG to return to normal in the other 4 patients with development delay ranged from 4 months to 2 years (mean = 375 days; median = 330 days). To the last follow-up, seizures were controlled well in 29 surviving patients, and 21 patients were able to deactivate from all medications without seizures recurrence. Sixteen patients showed varying degrees of developmental delay after onset. After seizure control, the psychomotor development was delayed in 7 patients (one died) until the last follow-up. Genetic analysis did not show any meaningful results.ConclusionAn observation period of 1–2 weeks is essential to identify patients with vitamin B6-responsive IS. The treatment time could be extended according to the treatment response and EEG changes. It might take a longer time for EEG to return to normal and to stop taking drugs in patients with persistent or unimproved developmental delay. Neurodevelopmental outcomes and prognosis of vitamin B6-responsive IS were relatively favorable.

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“…Vitamin B6 (pyridoxine) is an important cofactor in the process by which glutamic acid decarboxylase (GAD) converts the excitatory, pro-epileptogenic neurotransmitter, glutamate, into the inhibitory, anti-epileptogenic neurotransmitter, gamma-aminobutyric acid (GABA) [ 1 ]. This concept has been established in infants with pyridoxine-dependent epilepsy in addition to other causes of infantile spasms, with vitamin B6 administration resulting in the cessation of seizures [ 2 , 3 ]. Additionally, reports of adult patients with epilepsy subtypes other than pyridoxine-dependent epilepsy who presented with anti-seizure medication-resistant status epilepticus responded to pyridoxine administration with subsequent termination of seizures [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

“…Additionally, reports of adult patients with epilepsy subtypes other than pyridoxine-dependent epilepsy who presented with anti-seizure medication-resistant status epilepticus responded to pyridoxine administration with subsequent termination of seizures [ 4 ]. Given our knowledge of the role of vitamin B6 in the conversion of glutamate to GABA, its effect on seizure control in infants with specific epilepsy subtypes [ 2 , 3 ], reports of adult-onset seizures associated with vitamin B6 deficiency [ 1 , 5 , 6 ], and vitamin B6’s role in terminating status epilepticus in adult patients with other types of epilepsy [ 4 , 5 ], we suspect that low vitamin B6 levels in adult epilepsy patients may correlate with poor seizure control across all epilepsy subtypes. This study seeks to determine whether there is a relationship between pyridoxine levels and the level of seizure control in adults with epilepsy, regardless of their seizure type.…”

Section: Introductionmentioning

confidence: 99%

Low Serum Pyridoxine Levels Worsen Seizure Control in Adult Epilepsy Patients

Rane¹,

Elrahi²,

Villarreal³

et al. 2022

Cureus

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Background: Vitamin B6 (pyridoxine) is an important cofactor in the process by which glutamic acid decarboxylase (GAD) converts the excitatory, pro-epileptogenic neurotransmitter, glutamate, into the inhibitory, anti-epileptogenic neurotransmitter, gamma-aminobutyric acid (GABA). This concept has been established in infants with pyridoxine-dependent epilepsy as well as adult patients with other epilepsy subtypes who presented with medication-resistant status epilepticus, with both patient groups experiencing cessation of seizure activity following pyridoxine administration. Given our knowledge of the role of vitamin B6 in the conversion of glutamate to GABA, its effect on seizure control in infants with specific epilepsy subtypes, reports of adult-onset seizures associated with vitamin B6 deficiency, and vitamin B6’s role in terminating status epilepticus in adult patients with other types of epilepsy, we suspect that low vitamin B6 levels in adult epilepsy patients may correlate with poor seizure control across all epilepsy subtypes. This study seeks to determine whether there is a relationship between pyridoxine levels and the level of seizure control in adults with epilepsy, regardless of their seizure type. Methods: After obtaining institutional review board approval, we prospectively enrolled 32 patients (age range: 25-57 years) with epilepsy who presented to our clinic. Patients who did not meet the study criteria or who were diagnosed with psychogenic non-epileptic seizures (PNES) were excluded from the study (n = 2). Patients were classified as well-controlled (WC) or poorly controlled (PC) based on the absence or presence of a seizure within the last three months, respectively. After classification as WC or PC, pyridoxine serum levels and anti-seizure medication (ASM) levels were drawn in that clinic visit, following patient consent. All patients were contacted regarding pyridoxine and serum ASM levels, and patients that were found to be deficient in pyridoxine were treated with appropriate supplementation. At the end of the recruitment period, we performed analyses to determine if there was a statistically significant relationship between PC status and serum pyridoxine levels. Results: Of 32 patients, two patients were diagnosed with psychogenic non-epileptic events and were subsequently excluded. Of 30 patients, 10 had PC epilepsy. Median (interquartile range) serum B6 levels were 35.8 (26.8-54.2) in patients with WC epilepsy and 17.5 (10.1-41.3) in patients with PC epilepsy (P = 0.11). In the PC group, 6/10 (60%) of the patients demonstrated low serum pyridoxine compared to 3/20 (15%) in the WC group (P = 0.03). Conclusion: There was a statistically significant relationship between serum pyridoxine levels and seizure control. If appropriate, pyridoxine supplementation should be considered, especially in critically ill adult patients with refractory or PC seizures despite good adherence to ASMs.

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Pyridoxine Dependency: Report of a Case of Intractable Convulsions in an Infant Controlled by Pyridoxine

Cited by 371 publications

References 0 publications

A Rare Presentation Characterized by Epileptic Spasms in ALDH7A1, Pyridox(am)ine-5′-Phosphate Oxidase, and PLPBP Deficiency

A Rare Presentation Characterized by Epileptic Spasms in ALDH7A1, Pyridox(am)ine-5′-Phosphate Oxidase, and PLPBP Deficiency

The Clinical Features and Long-Term Follow-Up of Vitamin B6-Responsive Infantile Spasms in a Chinese Cohort

Low Serum Pyridoxine Levels Worsen Seizure Control in Adult Epilepsy Patients

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