Table 1: Summary of clinical, biochemical, neurophysiological findings with treatment and prognosis of vitamin responsive epileptic encephalopathies in children.

Usual age of onsetEtiologyBiochemical abnormalitiesType of epilepsyEEG findingsTreatmentPrognosis

Pyridoxine dependent epilepsy0–2 monthsALDH7A1 mutationElevated CSF/urine alpha aminoadipic semialdehyde; elevated CSF/plasma pipecolic acidFocal or generalized, myoclonic, epileptic spasmsNormal; Mild background slowing; generalized and multifocal epileptiform activities; hypsarrythmiaPyridoxine (IV followed by oral)Variable, dependent on early treatment with pyridoxine

Pyridoxal 5-phosphate dependent epilepsyEarly neonatalPNPO mutationHypoglycemia and lactic acidosis; elevated plasma glycine and threonine; elevated CSF L-Dopa and 3-methoxytyrosine; decreased CSF homovanillic acid and 5-hydroxyindoleacetic acidMultifocal myoclonic-tonicMultifocal sharp waves; Burst suppressionPyridoxal 5′-phosphate (Oral)High rate of mortality and poor neurocognitive outcome

Autoimmune folate antibody related epilepsy~4 monthsFolate antibody mediatedDecreased CSF 5-methyltetrahydrofolate; serum folate antibodiesEpileptic spasms, myoclonic-astatic seizures, absence, generalized tonic clonicMild diffuse slowing; multifocal spikes, hypsarrythmia, electrical status epilepticus of sleepFolinic acid (oral)Favorable outcome if treated before 6 years of age; incomplete neurological recovery if treated later

FOLR1 mutation related epilepsy4–8 yearsFOLR1 mutationDecreased CSF 5-methyltetrahydrofolateMyoclonic-astatic, myoclonic, generalized tonic clonicDiffuse slowing with multifocal spikesFolinic acid (oral)Favorable outcome if treated before 6 years of age; incomplete neurological recovery if treated later

Biotinidase deficiency2–5 months (Late onset adolescence to adulthood)Biotinidase gene mutationDecreased serum biotinidase; lactic acidosis; hyperammonemia; elevated 3-hydroxyisovalerate, 3-methylcrotonylglycine and methyl citrate; elevated CSF lactate and pyruvateGeneralized tonic clonic, myoclonic, partial seizures, infantile spasmsNormal; mild slowing; asynchrony, attenuated background; multifocal spikes; burst suppression; hypsarrythmiaBiotin (oral)Improved with treatment

B12 deficiencyInfantile DietaryElevated urine methylmalonic acidFocal or generalized, epileptic spasmsGeneralized slowing; focal or generalized epileptic discharges; hypsarrythmiaHydroxycobalamin or cyanocobalamin (IM)Preventable long-term sequelae with treatment