Abstracts

Rationale: Autosomal-recessive pyridox(am)ine phosphate oxidase (PNPO) deficiency causes pyridoxal-5-phosphate (PLP)-dependent epilepsy. Without rapid detection and specific intervention this causes catastrophic neonatal encephalopathy. We describe partial PNPO deficiency with a transient initial response to pyridoxine. An unidentified peak, thought to be pyridoxine phosphate, appears on the chromatographic system used to measure CSF PLP in PNPO-deficient patients receiving pyridoxine. Methods: CSF neurotransmitter metabolites, PLP and amino acids were analyzed while the patient was receiving pyridoxine. PNPO gene sequencing was performed by standard techniques. Results: A full-term 3220 gm newborn male presented with abnormal eye movements and grunting twelve hours following birth. EEG showed bilateral sharp discharges and episodic background suppression. MRI was unremarkable. Following trials of phenobarbital and levetiracetam, the patient became seizure-free for six weeks on pyridoxine. Breakthrough tonic seizures then occurred, followed by myoclonic and tonic-clonic seizures, unresponsive to topiramate and prednisolone. The seizures stopped upon the first dose of PLP but breakthrough events occurred as a dose became due. CSF PLP level was 23 nmol/l (normal range of 23-64 nmol/l). CSF amino acids showed a slight increase in threonine. Neurotransmitter metabolites were normal and there was no indication of biomarkers for pyridoxine responsive seizures. An unidentified peak was detected which has been noted in other PLP deficient patients supplemented with pyridoxine, and is suspected as representing pyridoxal phosphate based on the condensation of exogenous pyridoxine with kinases in the absence of the oxidase. Subsequent PNPO gene sequencing identified a homozygous mutation in a highly conserved area in exon 3: c.352G>A p.G118R, which predicts a substitution of arginine for glycine.Conclusions: Initial temporary pyridoxine responsiveness may be seen in partial PNPO deficiency. Partial pyridoxine responsiveness is an indication for possible PNPO deficiency and trial of pyridoxal-5-phosphate.