The patients with pyridoxine-dependent seizures (PDS) classically present with neonatal seizures, unresponsive to conventional anticonvulsant therapy but which can be controlled with pyridoxine monotherapy. Less commonly, later-onset cases present through the second to third year of life. In PDS, seizures are typically prolonged but can also include self-limiting partial, generalized, atonic, or myoclonic seizures or infantile spasms. Although most PDS patients show a rapid response to pyridoxine treatment, some show a transient response to common anticonvulsants or a poor initial response to pyridoxine.

PDS, a rare autosomal recessive disease, is caused by a deficiency of the enzyme alpha-aminoadipic semialdehyde dehydrogenase, encoded by the ALDH7A1 gene. Mutations in the ALDH7A1 gene and subsequent enzyme deficiency lead to an accumulation of alpha-aminoadipic semialdehyde (AASA) and a deficiency of the active form of vitamin B6, which is needed as a cofactor for many reactions in the central nervous system including metabolism of neurotransmitters such as dopamine, glutamate, GABA and serotonin.

Mutations in the ALDH7A1 gene account for ~95% of patients with PDS who have documented elevation of AASA. All individuals studied in families with the classic neonatal presentation have at least one mutation in the ALDH7A1 gene. The detection rate for individuals with atypical presentation of pyridoxine dependent seizures is not known.