Abstracts

Rationale: Pyridoxine-dependent epilepsy (PDE) is an autosomal recessive disorder resulting from mutations in the antiquitin gene. It is a neonatal epilepsy that responds effectively to pyridoxine treatment. However, it is often missed owing to lack of specific electrographic findings associated with the disorder.Methods: This is the case of a full-term infant, a product of a consanguinous marriage. Her birth history was unremarkable, and her delivery uncomplicated. Family history is remarkable for a sibling and cousin with PDE, resulting from a homozygous frameshift mutation in the ALDH7A1 gene after exon 16 (IVS16+5 G>A), which produced a premature stop codon. She presented to an outside hospital with first seizure of life on DOL 36. She was loaded with phenobarbital, and monitored on EEG for over 72 hours, but no anti-epileptics were started. She was then discharged and presented to our institution several days later with her fourth seizure of life. All of her seizures were brief, self-limited. The initial EEG at our institution showed excess sharp transients with one 20sec electrographic seizure over 72 hours. A pyridoxine challenge was discussed, but deferred as the EEG was so benign that it did not appear consistent with a pyridoxine-dependent epilepsy. She was instead started on keppra. A brain MRI showed: mega cisterna magna, corpus callosum hypoplasia, possible polymicrogyria. CSF biogenic amines were sent, and genetic testing was done, but the results became available after discharge. CSF showed low pyridoxal-5-phosphate, consistent with PDE. Genetic testing identified the familial mutation in ALDH7A1. PDE was diagnosed based on biochemical markers and genetic testing, despite not being suspected on EEG.Results: Benign EEG without clear electrographic activity specific to pyridoxine-dependent epilepsy resulted in delayed diagnosis of this patient with pyridoxine-dependent epilepsy. The diagnosis was confirmed with genetic testing which revealed the familial mutation in the antiquitin gene.Conclusions: Pyridoxine-dependent epilepsy is a disorder whose seizure component can be easily treated with pyridoxine supplementation. However, the diagnosis is oftentimes missed, or delayed, especially in cases whose EEGs appear benign. Genetic and molecular testing are helpful in making the diagnosis, but the delay in obtaining results from these modalities can be significant. Most, if not all, neonates with seizures should be screened for pyridoxine-dependent epilepsy and the initiation of pyridoxine supplementation should be seriously considered.