Pyridoxine Dependency
Pyridoxine dependency is an autosomal-recessive inborn error of metabolism. Pyridoxine dependency should be suspected in neonates with continuous seizures without an apparent cause. A history of unusual fetal movements (intrauterine convulsions) and meconium stained amniotic fluid is often present. An EEG pattern characterized by generalized bursts of synchronous high-voltage 1- to 4-Hz spike and wave complexes has been described.
The seizures in neonates with pyridoxine dependency are probably due to abnormal glutamate acid decarboxylase (GAD) and are probably caused by low concentrations of gamma-aminobutyric acid (GABA) and high concentrations of glutamic acid. Gamma-aminobutyric acid is an inhibitory neurotransmitter in the central nervous system, whereas glutamic acid is an excitatory neurotransmitter. The lack of sufficient pyridoxine to fully activate the abnormal GAD leads to decreased activity of glutamate acid decarboxylase; the low activity of glutamate decarboxylase decreases the conversion of glutamate to GABA. Other possible cause of pyridoxine dependent seizures is the failure of pyridoxine to become pyridoxal phosphate. Pyridoxal phosphate is the active form of pyridoxine.
The diagnosis of pyridoxine dependency is made on the basis of the response to intravenous pyridoxine (pyridoxal phosphate). Low levels of pyridoxal-5-phosphate and high levels of pipecolic acid in the CSF can occur in patients with pyridoxine dependent seizures.
Treatment consists of pyridoxine 100 mg intravenously. The convulsions and abnormal electroencephalographic seizure pattern usually stop immediately. Neonates should be monitored during, and for about one hour after, the infusion of pyridoxine because hypotonia and apnea may occur in neonates with pyridoxine dependency. This first-dose effect of pyridoxine in patients with pyridoxine dependency is probably due to a burst of GABA synthesis that results from sudden activation of glutamate decarboxylase.Intravenous therapy should be followed by oral pyridoxine 5 to 15 mg/kg per day. Patients taking oral pyridoxine should be evaluated periodically for the possibility of neuropathy. Pregnant mothers of infants with pyridoxine-dependent seizures should receive pyridoxine 100 mg/day during the final half of gestation.

Folinic Acid Responsive Seizures
Neonates with onset of seizures during the first week of life and no explanation for seizures may have folinic acid responsive seizures. This type of seizure may be associated with an abnormal peak in the CSF electrophoresis. Treatment with folinic acid 2.5 to 5 mg twice daily stops the seizures.

Biotinidase deficiency
Biotinidase is the enzyme that cleaves biotin from biocytin and byotinyl peptides. Biotin is needed for the activation of mitochondrial carboxylases (propionyl-CoA carboxylase, pyruvate carboxylase, and beta methylcrotonyl-CoA carboxylase). No biotinidase leads to no biotin. No biotin leads to no activity of the previously mentioned carboxylases. Lack of activity of the mitochondrial carboxylases leads to metabolic derangement and to seizures. Neonates with seizures due to biotinidase deficiency usually have skin rash, total or partial alopecia, and persistent conjunctivitis. The diagnosis is suspected by the specific pattern of urine organic acid reflecting the deficiencies of propionyl-CoA carboxylase, pyruvate carboxylase, and beta methylcrotonyl-CoA carboxylase. The diagnosis is confirmed by measuring biotinidase activity in blood serum. Treatment consists of biotin 5 to 20 mg orally each day.

Disorder of glucose transport
Glucose is transported across the blood brain barrier by facilitative diffusion. Glut-1 protein is a major transporter. A defect in this transporter leads to low cerebrospinal fluid glucose and lactate. The possibility of a disorder of glucose transport should be considered when the cerebrospinal fluid glucose concentration is less than about 50% of the serum glucose concentration and the CSF lactic acid is low.Treatment with a ketogenic diet controls seizures and prevents neurological deficit.

Sulfite oxidase deficiency
Sulfite oxidase deficiency, alone or combined with xanthine oxidase deficiency (molybdenum cofactor deficiency) may produce neonatal seizures. Urine uric acid may be low in molybdenum cofactor deficiency. Elevated plasma or urine S-sulfocysteine is diagnostic. These aminoacids have to be requested by name since they will not be detected by routine aminoacid or organic acid determinations. There is no specific therapy.

GABA transaminase deficiency
Four-aminobutyrate aminotransferase (GABA-transaminase) is the enzyme that catalyzes the conversion of GABA to succinic acid. The diagnosis is established by elevated GABA levels in plasma or CSF (it seems paradoxical that seizures would be produced by elevated GABA, since GABA is an inhibitory neurotransmitter). Agenesis of the corpus callosum and cerebellar hypoplasia was reported in a patient.

GAMT deficiency
Guanidinoacetate methyltransferase (GMAT) deficiency is suspected by the MRI spectroscopy finding of an absence of creatine/creatine phosphate peak, generalized elevation of serum amino acids when calculated relative to creatinine, by low plasma creatinine levels. Guanidinoacetate methyltransferase (GMAT) deficiency is diagnosed by elevated guanidinoacetate (assayed by tandem-mass spectroscopy). Treatment with creatinine monohydrate (400 to 500 mg/kg per day) has proven effective.