A full term female with an uncomplicated pregnancy and delivery had onset of focal motor seizures at 1 hour of life. On day of life (DOL) 5, she developed episodes of erratic saccadic eye movements associated with head jerks without electrographic correlate.  She was discharged home on phenobarbital and had resolution of abnormal eye movements on DOL 10.

On DOL 13, she had re-emergence of 1-5 minute-long episodes of erratic saccadic eye movements with associated head jerks. They were not associated with altered consciousness or other abnormal movements. The saccade-head movement was in the same direction with a brief interval fixation as if ‘following a fly,’ appearing erratic. Seizures recurred and progressed to status epilepticus on DOL 16. Ketogenic diet was initiated due to concern for GLUT-1 deficiency, however, cerebrospinal fluid (CSF) analysis revealed mild hypoglycorrhachia (46 g/dL) with a borderline low CSF:serum glucose ratio of 0.52, low CSF P5P, and genetic testing with 1 known pathogenic variant and 1 variant of uncertain significance in the PNPO gene, confirmed to be in trans. A diagnosis of pyridoxal-5’-phosphate dependent epilepsy was made with partial response to pyridoxine and full resolution of seizures with addition of P5P.  

The differential for neonatal seizures associated with chaotic, aberrant coordinated saccades and head movements should be broadened to include PNPO-associated epilepsy, particularly when CSF analysis is borderline or inconsistent with GLUT-1 deficiency syndrome. Further characterization of eye movements seen in pyridoxal-5’-phosphate dependent epilepsy may aid in early identification and treatment of this vitamin-responsive epilepsy.