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Review
. 2021 Dec 31;12(1):65.
doi: 10.3390/brainsci12010065.

Pyridoxine-Dependent Epilepsy and Antiquitin Deficiency Resulting in Neonatal-Onset Refractory Seizures

Konrad Kaminiów  1 , Magdalena Pająk  1 , Renata Pająk  1 , Justyna Paprocka  2
Affiliations
Review

Pyridoxine-Dependent Epilepsy and Antiquitin Deficiency Resulting in Neonatal-Onset Refractory Seizures

Konrad Kaminiów et al. Brain Sci. .

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.

Keywords: ALDH7A1; inborn errors of metabolism; metabolic epilepsy; pyridoxine-dependent epilepsy; seizures.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Simplified diagram of lysine metabolism with detailed (red markings) changes occurring in this cycle in pyridoxine-dependent epilepsy. The red rectangle indicates the main problem underlying the PDE, i.e., binding of the active form of vitamin B6 (pyridoxal-5-phosphate) by intermediate metabolites of lysine catabolism (Δ1-piperideine-6-carboxylate) [1,2,16,17,18,19].
See this image and copyright information in PMC

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