Effect of dietary lysine restriction and arginine supplementation in two patients with pyridoxine-dependent epilepsy

Yuzyuk, Tatiana; Thomas, Amanda; Viau, Krista; Liu, Aiping; Biase, Irene De; Botto, Lorenzo D.; Pasquali, Marzia; Longo, Nicola

doi:10.1016/j.ymgme.2016.04.015

Cited by 29 publications

(39 citation statements)

References 25 publications

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“…Some reports suggest further reduced toxic metabolites in the blood, urine, and cerebrospinal fluid, and possible improvement of neurodevelopmental outcomes, but this has not been confirmed. 16,27 Consistent with previous reports, 7 abnormal biochemical and plasma amino acids and urine organic acids test results were not found to be specific in this series.…”

Section: Discussionsupporting

confidence: 91%

“…4 To date, more than 280 patients with PDE-ALDH7A and 27 with PDE-PLPBP have been reported. [4][5][6][7][8][9][10][11][12][13][14][15][16] Here, we report the clinical, electrophysiological, biochemical, and genetic spectrum of 33 patients with PDE from 31 unrelated families, including 12 patients (patient 1-6, patient 8-13) who were reported previously. [17][18][19] Thirty-one patients were PDE-ALDH7A1, and the other two patients were PDE-PLPBP.…”

mentioning

confidence: 94%

“…Subsequently, mutations in PLPBP (previously called PROSC ) encoding PLP binding protein were identified in 2016, resulting in impaired cellular PLP homeostasis . To date, more than 280 patients with PDE‐ ALDH7A and 27 with PDE‐ PLPBP have been reported …”

mentioning

confidence: 99%

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Clinical and genetic features in pyridoxine‐dependent epilepsy: a Chinese cohort study

Jiao

Jin

Gong

et al. 2019

Develop Med Child Neuro

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ABBREVIATIONS a-AASA a-aminoadipic semialdehyde AED Antiepileptic drugs P6C Piperideine-6-carboxylic PDE Pyridoxine-dependent epilepsy PLP Pyridoxal 5 0 -phosphate AIM To characterize the clinical and genetic characteristics of a large cohort of patients with pyridoxine-dependent epilepsy (PDE). METHOD We retrospectively collected clinical and genetic information of 33 (15 males, 18 females; mean [SD] age 4y 11mo [2y 5mo]; 1y 3mo-10y 4mo) patients with PDE from 31 unrelated families at a single centre.RESULTS There were many types of seizures, with focal seizures in 32 cases. Dravet syndrome was suspected clinically in two patients. Electroencephalogram (EEG) was normal in seven patients at the initial stage and then in 17 patients during pyridoxine maintenance therapy. Genetic studies revealed 26 kinds of variants in ALDH7A1 and four in PLPBP with 18 variants unreported previously, and 48 ALDH7A1 variants were located in exon 11, 12, 14, and 17 or intron 9 and 11. In addition, three patients carried different exons deletion. Among these, seizures could be controlled for several years in one patient by levetiracetam monotherapy. Another patient remained seizure free for up to 7 months without therapy. All patients received oral pyridoxine treatment, with only one case (with exon 8-13 deletion) showing poor control. INTERPRETATION This study illustrates the range of clinical presentations and genetic causesin PDE, as well as responsiveness to antiepileptic drugs. A relationship between EEG and pyridoxine therapy could be seen in many cases. Seizure control was seen in all with pyridoxine monotherapy except for one patient.

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Section: Discussionsupporting

confidence: 91%

mentioning

confidence: 94%

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Clinical and genetic features in pyridoxine‐dependent epilepsy: a Chinese cohort study

Jiao

Jin

Gong

et al. 2019

Develop Med Child Neuro

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“…“Triple therapy” (pyridoxine and arginine supplementation, lysine restriction) has been reported for nine patients . Treatment reduced levels of biomarkers such as plasma AASA, P6C, pipecolic acid, and threonine and improved development.…”

Section: Deficiency Of Aldh7a1mentioning

confidence: 99%

“…"Triple therapy" (pyridoxine and arginine supplementation, lysine restriction) has been reported for nine patients. [77][78][79] Treatment reduced levels of biomarkers such as plasma AASA, P6C, pipecolic acid, and threonine and improved development. Optimum results were reported for patients where treatment was started early, however, larger cohorts and long-term data with neurocognitive testing are needed to provide robust data.…”

Section: Deficiency Of Aldh7a1mentioning

confidence: 99%

Disorders affecting vitamin B₆ metabolism

Wilson¹,

Plecko²,

Mills³

et al. 2019

J of Inher Metab Disea

169

193

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Vitamin B6 is present in our diet in many forms, however, only pyridoxal 5′‐phosphate (PLP) can function as a cofactor for enzymes. The intestine absorbs nonphosphorylated B6 vitamers, which are converted by specific enzymes to the active PLP form. The role of PLP is enabled by its reactive aldehyde group. Pathways reliant on PLP include amino acid and neurotransmitter metabolism, folate and 1‐carbon metabolism, protein and polyamine synthesis, carbohydrate and lipid metabolism, mitochondrial function and erythropoiesis. Besides the role of PLP as a cofactor B6 vitamers also play other cellular roles, for example, as antioxidants, modifying expression and action of steroid hormone receptors, affecting immune function, as chaperones and as an antagonist of Adenosine‐5'‐triphosphate (ATP) at P2 purinoceptors. Because of the vital role of PLP in neurotransmitter metabolism, particularly synthesis of the inhibitory transmitter γ‐aminobutyric acid, it is not surprising that various inborn errors leading to PLP deficiency manifest as B6‐responsive epilepsy, usually of early onset. This includes pyridox(am)ine phosphate oxidase deficiency (a disorder affecting PLP synthesis and recycling), disorders affecting PLP import into the brain (hypophosphatasia and glycosylphosphatidylinositol anchor synthesis defects), a disorder of an intracellular PLP‐binding protein (PLPBP, previously named PROSC) and disorders where metabolites accumulate that inactivate PLP, for example, ALDH7A1 deficiency and hyperprolinaemia type II. Patients with these disorders can show rapid control of seizures in response to either pyridoxine and/or PLP with a lifelong dependency on supraphysiological vitamin B6 supply. The clinical and biochemical features of disorders leading to B6‐responsive seizures and the treatment of these disorders are described in this review.

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Identification of a novel biomarker for pyridoxine‐dependent epilepsy: Implications for newborn screening

Wempe

Kumar

et al. 2019

J of Inher Metab Disea

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Pyridoxine-dependent epilepsy (PDE) is often characterized as an early onset epileptic encephalopathy with dramatic clinical improvement following pyridoxine supplementation. Unfortunately, not all patients present with classic neonatal seizures or respond to an initial pyridoxine trial, which can result in the under diagnosis of this treatable disorder. Restriction of lysine intake and transport is associated with improved neurologic outcomes, although treatment should be started in the first year of life to be effective. Because of the documented diagnostic delay and benefit of early treatment, we aimed to develop a newborn screening method for PDE. Previous studies have demonstrated the accumulation of Δ 1 -piperideine-6-carboxylate and α-aminoadipic semialdehyde in individuals with PDE, although these metabolites are unstable at room temperature (RT) limiting their utility for newborn screening. As a result, we sought to identify a biomarker that could be applied to current newborn screening paradigms. We identified a novel metabolite, 6-oxopipecolate (6-oxo-PIP), which accumulates in substantial amounts in blood, plasma, urine, and cerebral spinal fluid of individuals with PDE. Using a stable isotope-labeled internal standard, we developed a nonderivatized liquid chromatography tandem mass spectrometry-based method to quantify 6-oxo-PIP. This method replicates the analytical techniques used in many laboratories and could be used with few modifications in newborn screening programs. Furthermore, 6-oxo-PIP was measurable in urine for 4 months even when stored at RT. Herein, we report a novel biomarker for PDE that is stable at RT and can be quantified using current newborn screening techniques. K E Y W O R D S6-hydroxy-pipecolate, 6-oxo-pipecolate, ALDH7A1, alpha aminoadipic semialdehyde, pyridoxinedependent epilepsy

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Effect of dietary lysine restriction and arginine supplementation in two patients with pyridoxine-dependent epilepsy

Cited by 29 publications

References 25 publications

Clinical and genetic features in pyridoxine‐dependent epilepsy: a Chinese cohort study

Clinical and genetic features in pyridoxine‐dependent epilepsy: a Chinese cohort study

Disorders affecting vitamin B₆ metabolism

Identification of a novel biomarker for pyridoxine‐dependent epilepsy: Implications for newborn screening

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Effect of dietary lysine restriction and arginine supplementation in two patients with pyridoxine-dependent epilepsy

Cited by 29 publications

References 25 publications

Clinical and genetic features in pyridoxine‐dependent epilepsy: a Chinese cohort study

Clinical and genetic features in pyridoxine‐dependent epilepsy: a Chinese cohort study

Disorders affecting vitamin B6 metabolism

Identification of a novel biomarker for pyridoxine‐dependent epilepsy: Implications for newborn screening

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Disorders affecting vitamin B₆ metabolism