Abstract
Pyridoxine-dependent epilepsy (PDE) is an autosomal recessive neurometabolic disorder due to a deficiency of α-aminoadipic semialdehyde dehydrogenase (mutation in ALDH7A1 gene), more commonly known as antiquitin (ATQ). ATQ is one of the enzymes involved in lysine oxidation; thus, its deficiency leads to the accumulation of toxic metabolites in body fluids. PDE is characterized by persistent, recurrent neonatal seizures that cannot be well controlled by antiepileptic drugs but are responsive clinically and electrographically to daily pyridoxine (vitamin B6) supplementation. Although the phenotypic spectrum distinguishes between typical and atypical, pyridoxine-dependent is true for each. Diagnosis may pose a challenge mainly due to the rarity of the disorder and the fact that seizures may not occur until childhood or even late adolescence. Moreover, patients may not demonstrate an obvious clinical or electroencephalography response to the initial dose of pyridoxine. Effective treatment requires lifelong pharmacologic supplements of pyridoxine, and dietary lysine restriction and arginine enrichment should improve prognosis and avoid developmental delay and intellectual disability. The purpose of this review is to summarize briefly the latest reports on the etiology, clinical symptoms, diagnosis, and management of patients suffering from pyridoxine-dependent epilepsy.
Highlights
Refractory status epilepticus (RSE), which is a status epilepticus (SE) that does not respond to adequately used first- and second-line antiepileptic drugs, as well as superrefractory status epilepticus (SRSE), which can be diagnosed if the status epilepticus lasts over 24 h or when it persists after inducing coma or recurs after its ending, can both appear in Pyridoxine-dependent epilepsy (PDE)
For seizures that respond to vitamin B6 treatment but no biochemical or molecular markers of PDE are found, further diagnostics should be performed for the conditions broadly discussed in the differential diagnosis section, such as pyridoxal phosphate responsive epileptic encephalopathy, caused by deficiency of pyridoxamine 50 -phosphate oxidase (PNPO); tissue-nonspecific alkaline phosphatase (TNSALP) deficiency; familial hyperphosphatasia (PIGV deficiency) and hyperprolinemia type II [1,15,17,30,31,32]
Prenatal supplementation of pyridoxine in the fetus at risk or confirmed with PDE was shown to be effective in preventing seizures, and in some cases, it resulted in suitable further development of patients [55]
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Pyridoxine-dependent epilepsy (PDE) is classically diagnosed in newborns with seizures responsive to pyridoxine and resistant to anti-seizure medication It can, have an atypical manifestation, with later onset, in which patients do not respond to pyridoxine immediately, but their seizures can be controlled if pyridoxine therapy is continued for several months. Refractory status epilepticus (RSE), which is a status epilepticus (SE) that does not respond to adequately used first- and second-line antiepileptic drugs, as well as superrefractory status epilepticus (SRSE), which can be diagnosed if the status epilepticus lasts over 24 h or when it persists after inducing coma or recurs after its ending, can both appear in PDE These conditions usually present with generalized convulsive SE or focal. Other substances have been tested on animal models (nitric oxide; with highly contradictory results, its effect depends on the epilepsy type) and on brain cells, obtained from patients (ifendopril reduces neural excitability, in animal models alleviates the behavioral manifestations) [7,8,9]
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