The Pediatric Neurotransmitter Disorders

Abstract

The pediatric neurotransmitter disorders represent an enlarging group of neurological syndromes characterized by abnormalities of neurotransmitter synthesis and breakdown. The disorders of dopamine and serotonin synthesis are aromatic amino acid decarboxylase deficiency, tyrosine hydroxylase deficiency, and disorders of tetrahydrobiopterin synthesis. Amino acid decarboxylase, tyrosine hydroxylase, sepiapterin reductase, and guanosine triphosphate cyclohydrolase (Segawa disease) deficiencies do not feature elevated serum phenylalanine and require cerebrospinal fluid analysis for diagnosis. Segawa disease is characterized by dramatic and lifelong responsiveness to levodopa. Glycine encephalopathy is typically manifested by refractory neonatal seizures secondary to a defect of the glycine degradative pathway. gamma-amino butyric acid (GABA) metabolism is associated with several disorders, including glutamic acid decarboxylase deficiency with nonsyndromic cleft lip/ palate, GABA-transaminase deficiency, and succinic semialdehyde dehydrogenase deficiency. The latter is characterized by elevated gamma-hydroxybutyric acid and includes a wide range of neuropsychiatric symptoms as well as epilepsy. Pyridoxine-dependent seizures have now been associated with deficiency of alpha-aminoadipic semialdehyde dehydrogenase, as well as a new variant requiring therapy with pyridoxal-5-phosphate, the biologically active form of pyridoxine.

Neonatal Seizures and Inborn Errors of Metabolism: An Update

“…To date, they are defined as that group of disorders due to defects of the respiratory chain complexes [34]. Epilepsy has been associated to 26-60% of all mitochondrial disorders, however, few of them show neonatal onset [33,34].…”

“…Oxidative phosphorylation (OXPHOS) disorders may present in the neonatal period [6,33,34]. The OXPHOS system comprises the mitochondrial respiratory chain complexes (complexes I-IV) and adenosine triphosphatase (complex V) [34].…”

“…The OXPHOS system comprises the mitochondrial respiratory chain complexes (complexes I-IV) and adenosine triphosphatase (complex V) [34]. In newborns, deficiency of complex I, II, and IV have been reported [34].…”

“…The OXPHOS system comprises the mitochondrial respiratory chain complexes (complexes I-IV) and adenosine triphosphatase (complex V) [34]. In newborns, deficiency of complex I, II, and IV have been reported [34]. Features of OXPHOS disorders at birth and before include fetal hydrops, IUGR, prematurity, respiratory disturbances, poor feeding, vomiting, lactic acidosis, and lack of a symptom free interval following birth [6,33].…”

“…Features of OXPHOS disorders at birth and before include fetal hydrops, IUGR, prematurity, respiratory disturbances, poor feeding, vomiting, lactic acidosis, and lack of a symptom free interval following birth [6,33]. Newborns with neurologic and behavioral deterioration, lethargy and seizures that present with marked lactic acidosis in blood and CSF are suspected to have OXPHOS deficiency [34]. MRI in newborns may be less indicative than infants that usually shows Leigh syndrome features.…”