Pyridoxine dependent epilepsy: Is late onset a predictor for favorable outcome?

Rooy, R. L. P. de; Halbertsma, F.J.; Struijs, Eduard A.; Spronsen, Francjan J. van; Lunsing, Roelineke J.; Schippers, H. M.; Hasselt, Peter M. van; Plecko, Barbara; Wohlrab, Gabriele; Whalen, Sandra; Benoist, J.-F.; Valence, Stéphanie; Mills, Philippa B.; Bok, Levinus A.

doi:10.1016/j.ejpn.2018.03.009

Cited by 16 publications

(29 citation statements)

References 13 publications

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“…7,8,47,48 Late seizure onset has been postulated as beneficial for the developmental outcome with several factors hypothesized to contribute to this outcome including genetic and functional variation, variation in the treatment regimen, absence of neonatal seizures, and unknown protective factors. 27,49 3.3 | Diagnostic investigations The initial guideline recommendations stated that PDE-ALDH7A1 should be considered in some clinical scenarios including seizures of unknown etiology, infants and children with seizures which are partially responsive to antiseizure medications, and children under 1 year of age without an apparent causal brain malformation. 25 Since those initial guidelines were published, some patients have presented after 1 year of age and into late adolescence.…”

Section: Consensus Proceduresmentioning

confidence: 99%

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Consensus guidelines for the diagnosis and management of pyridoxine‐dependent epilepsy due to α‐aminoadipic semialdehyde dehydrogenase deficiency

Coughlin

Tseng

Abdenur

et al. 2020

J of Inher Metab Disea

130

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Pyridoxine‐dependent epilepsy (PDE‐ALDH7A1) is an autosomal recessive condition due to a deficiency of α‐aminoadipic semialdehyde dehydrogenase, which is a key enzyme in lysine oxidation. PDE‐ALDH7A1 is a developmental and epileptic encephalopathy that was historically and empirically treated with pharmacologic doses of pyridoxine. Despite adequate seizure control, most patients with PDE‐ALDH7A1 were reported to have developmental delay and intellectual disability. To improve outcome, a lysine‐restricted diet and competitive inhibition of lysine transport through the use of pharmacologic doses of arginine have been recommended as an adjunct therapy. These lysine‐reduction therapies have resulted in improved biochemical parameters and cognitive development in many but not all patients. The goal of these consensus guidelines is to re‐evaluate and update the two previously published recommendations for diagnosis, treatment, and follow‐up of patients with PDE‐ALDH7A1. Members of the International PDE Consortium initiated evidence and consensus‐based process to review previous recommendations, new research findings, and relevant clinical aspects of PDE‐ALDH7A1. The guideline development group included pediatric neurologists, biochemical geneticists, clinical geneticists, laboratory scientists, and metabolic dieticians representing 29 institutions from 16 countries. Consensus guidelines for the diagnosis and management of patients with PDE‐ALDH7A1 are provided.

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Section: Consensus Proceduresmentioning

confidence: 99%

Section: Clinical Presentationmentioning

confidence: 99%

Consensus guidelines for the diagnosis and management of pyridoxine‐dependent epilepsy due to α‐aminoadipic semialdehyde dehydrogenase deficiency

Coughlin

Tseng

Abdenur

et al. 2020

J of Inher Metab Disea

130

View full text Add to dashboard Cite

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“…Her first convulsions occurred at 2 months, whereas 75-89% of patients present seizure before 28 days [11]. Neurological prognosis is often poor even in late-onset PDE [15], patients show a developmental delay, with a lower verbal IQ than the performance IQ, unlike our patient (Baxter2001 ). Several studies did not show correlations between genotype and phenotype [1,11,16].…”

Section: Discussionmentioning

confidence: 59%

“…We present a female patient with a late-onset PDE (this phenotype has been described by [15] and [7]). Her first convulsions occurred at 2 months, whereas 75-89% of patients present seizure before 28 days [11].…”

Section: Discussionmentioning

confidence: 99%

Clinical and biochemical outcome of a patient with pyridoxine-dependent epilepsy treated by triple therapy (pyridoxine supplementation, lysine-restricted diet, and arginine supplementation)

et al. 2020

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Pyridoxine-dependent epilepsy (PDE) is a recessive genetic disease characterized by epileptic encephalopathy with therapeutic response to pharmacological doses of pyridoxine and resistance to anti-epileptic treatments. The recent discovery in 2006 of the genetic defect antiquitin (ALDH7A1, OMIM #266100) has helped to understand the underlying mechanism, which is the accumulation of neurotoxic intermediates in the lysine catabolic pathway. The goal of the new therapeutic approach, termed triple therapy (TT) (pyridoxine, lysine-restricted diet and arginine supplementation), is to improve epilepsy control and neurocognitive development in patients with PDE. We present the 3-year treatment outcome for a child with PDE on pyridoxine treatment (started at age 5 months), lysine-restricted diet (started at age 17 months) and arginine supplementation therapy (started at age 19 months). The TT was well-tolerated with good compliance. No adverse events were reported. We observed a neurodevelopmental improvement, significantly fewer seizures, and a reduction of pipecolic acid (PA) as a biomarker of the illness. Our results show an improving clinical evolution, supporting and extending previous studies reporting efficacy of TT.

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“…Alternatively, it is possible that the assays used do not reflect endogenous residual activity. Ultimately, cognitive outcome may largely depend on phenotypic variability, as opposed to age of diagnosis and treatment, as IQ tends to be higher in patients with late onset PDE than with classic early onset . However, the wide spectrum of cognitive outcomes in patients with PDE may be a result of multiple interacting factors.…”

Section: Discussionmentioning

confidence: 99%

Diagnosis of pyridoxine‐dependent epilepsy in an adult presenting with recurrent status epilepticus

et al. 2019

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Pyridoxine-dependent epilepsy (PDE) is a genetic metabolic disease caused by inborn errors affecting vitamin B6 metabolism, which typically presents with neonatal seizures resistant to antiepileptic drugs (AEDs). Treatment with pyridoxine terminates seizures and prevents neurological decline. We describe a case in which the diagnosis was established at the age of 22 years. Birth and development were normal, but there was a history of three isolated tonic-clonic seizures during childhood and adolescence. At the age of 18 years, she developed frequent focal motor seizures, many evolving into tonic-clonic seizures. Electroencephalography identified a focus in the posterior right hemisphere, but magnetic resonance imaging of the brain was normal. Over the next 3 years, she was hospitalized with uncontrolled seizures on six occasions and spent a total of 121 days in intensive care. The seizures proved resistant to 12 different AEDs. Exome sequencing revealed two pathogenic mutations in ALDH7A1. Since starting on pyridoxine 50 mg once daily, she has been seizure-free, all AEDs have been withdrawn, and cognition has improved to premorbid levels.This case illustrates the importance of considering PDE in drug-resistant epilepsy in adults. K E Y W O R D Sgenetic, metabolic, pyridoxine e2 | OSMAN et Al.

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Pyridoxine dependent epilepsy: Is late onset a predictor for favorable outcome?

Abstract: We suggest that favorable outcome in late onset PDE might be explained by a combination of factors. A yet unknown protective factor, different genetic variations, functional variation and secondarily variation in treatment regimens and absence of neonatal seizure induced brain damage.

Cited by 16 publications

References 13 publications

Consensus guidelines for the diagnosis and management of pyridoxine‐dependent epilepsy due to α‐aminoadipic semialdehyde dehydrogenase deficiency

Consensus guidelines for the diagnosis and management of pyridoxine‐dependent epilepsy due to α‐aminoadipic semialdehyde dehydrogenase deficiency

Clinical and biochemical outcome of a patient with pyridoxine-dependent epilepsy treated by triple therapy (pyridoxine supplementation, lysine-restricted diet, and arginine supplementation)

Diagnosis of pyridoxine‐dependent epilepsy in an adult presenting with recurrent status epilepticus

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