Alpha-aminoadipic semialdehyde (alpha-AASA) dehydrogenase deficiency was shown to cause pyridoxine-dependent epilepsy in a considerable number of patients. alpha-AASA dehydrogenase deficiency is an autosomal recessive disorder characterized by a neonatal-onset epileptic encephalopathy in which seizures are resistant to antiepileptic drugs but respond immediately to the administration of pyridoxine. Increased plasma and urinary levels of alpha-AASA are associated with pathogenic mutations in the alpha-AASA dehydrogenase (ALDH7A1/antiquitin) gene.
In a study by Plecko et al. involving 18 patients with neonatal seizure onset, the c.1279G>C mutation in the ALDH7A1 gene, accounted for 12 of 36 alleles. This variant results in a p.Glu427Gln substitution. In vitro functional expression studies in hamster ovary cells showed that the mutant enzyme had no detectable activity.
Salomons et al. identified a homozygous 1279G>C mutation in 7 Dutch patients from 4 apparently unrelated families with pyridoxine-dependent epilepsy.