Mutation of the ALDH7A1 gene in a patient with pyridoxal phosphate-dependent neonatal epileptic encephalopathy: a clinical case

Abstract

The article presents a clinical case of severe infantile generalized idiopathic epilepsy with status-like seizures, muscular dystonia and developmental delay. The examination included a phenotypic analysis: the course of the perinatal period, the nature of seizures, cognitive and behavioral disorders; video electroencephalography, and brain MRI. Using the targeted exome sequencing of genes associated with epileptic encephalopathy (NGS), we detected a nucleotide heterozygous variant of the ALDH7A1 gene (previously not described). This mutation led to the appearance of a stop codon in position 82 of the protein p.Arg82Ter and the amino acid substitution in position 399 of the protein p.Glu399Gln. This clinical observation demonstrates the importance of DNA-based diagnosis involving the targeted exome sequencing to identify molecular defects, especially in severe neonatal drug-resistant seizures. In the case of confirmed mutations in the ALDH7A1 gene, the patient should be given vitamin B6 at the therapeutic doses for seizure relief.