Two neonates with pyridoxine-dependent epilepsy and significant elevation of pipecolic acid in plasma and CSF are reported from the University Hospital Vienna, Austria. Diagnosis was based on an immediate control of seizures and clinical response with IV pyridoxine 100 to 300 mg, and continued control of seizures with a maintenance oral dose of 200 mg/day or 10 mg/kg/d. Further increases of CSF pipecolic acid occurred during a 72-hour withdrawal of pyridoxine in 1 patient. Pipecolic acid was continuously elevated in the plasma of the 2 infants with pyridoxine-dependent epilepsy (10 mcmol/L plasma), and was normal in 26 controls with non-pyridoxine-dependent seizures (2 mcmol/L). There was an inverse correlation of pyridoxalphosphate in plasma versus pipecolic acid levels. High pipecolic acid levels are suggested as a diagnostic marker of pyridoxine-dependent epilepsy. 
COMMENT. Plasma pipecolic acid determination may aid in diagnosis, and a persistent elevation may avoid premature pyridoxine withdrawal in infants with pyridoxine-dependent epilepsy (normal range, 0.7-2.6 mcmol/L). The authors report an additional case of this syndrome in a 7 year-old child.
Pipecolic acid elevation in pyridoxine-dependent epilepsy may be caused by a deficiency of pyridoxal-dependent a-aminoadipic acid transaminase, a step in the degradation of lysine to acetoacetyl-CoA in the brain. Pipecolic acid also accumulates in peroxisomal disorders, such as Zellweger syndrome.