levoleucovorin and Metabolism--Inborn-Errors

Metabolic disorders constitute an important cause of neurologic disease, including neonatal epilepsy. Epilepsy rarely dominates the clinical presentation, which is more frequently associated with other neurologic symptoms, such as hypotonia and/or vigilance disturbances. In most cases, epilepsy secondary to inherited metabolic disorders presents with polymorphic clinical and electrographic features that are difficult to classify into precise epileptic syndromes. However, specific types of seizures, such as myoclonic seizures or distinctive electroencephalographic patterns, such as suppression burst patterns, epileptic syndrome or early myoclonic encephalopathy, may suggest a specific metabolic disease. The aim of this article is to help clinicians in reviewing potential metabolic diagnoses and approaching metabolic evaluations.

Topics: Age Factors; Anticonvulsants; Biotin; Brain; Electroencephalography; Epilepsies, Myoclonic; Epilepsy; gamma-Aminobutyric Acid; Humans; Infant, Newborn; Leucovorin; Metabolism, Inborn Errors; Pyridoxine; Seizures; Time Factors; Vitamin B Complex

Seizures are one of the most frequently occurring neurologic phenomena in childhood; an inborn error of metabolism should always be considered in the diagnostic workup of patients with seizures after more common causes have been excluded. Many of the known inborn metabolic errors associated with seizures can be detected by metabolite measurement in urine or blood. It is now recognized, however, that there are several conditions in which peripheral metabolite profiles remain normal. Abnormal metabolism is indicated only by the accumulation or absence of specific metabolites within the central nervous system. Some of these disorders can be detected by in vivo magnetic resonance spectroscopy. More often, an etiology can be ascertained only by analysis of specific metabolites in cerebrospinal fluid. This review describes the utility of cerebrospinal fluid metabolite analysis in the differential diagnosis of inborn errors of metabolism that lead to infantile epilepsy. These include disorders of central nervous system energy metabolism, creatine synthesis and transport, serine biosynthesis, and glucose transport, together with defects affecting the gamma-aminobutyric acid (GABA), catecholamine, and serotonin neurotransmitter systems. In addition, information is provided regarding detection of an early-onset seizure disorder that responds to folinic acid.

Topics: Anticonvulsants; Biogenic Amines; Biomarkers; Clinical Laboratory Techniques; Humans; Infant; Leucovorin; Metabolism, Inborn Errors; Spasms, Infantile; Spinal Puncture; Treatment Outcome

This report presents a male who developed clonic seizures on the day he was born. The next day, the diagnosis of pyridoxine-dependent seizures was made. However, contradictory to this diagnosis, seizures reappeared despite treatment with pyridoxine. Seizures ceased after folinic acid was initiated. The clinical and biochemical characteristics of folinic acid-responsive seizures are reviewed. Treatment with folinic acid should be considered in neonatal seizures of unknown origin that do not respond to pyridoxine, or manifest a transient response to pyridoxine.

Topics: Epilepsy; Humans; Infant; Infant, Newborn; Leucovorin; Male; Metabolism, Inborn Errors; Pyridoxine; Treatment Outcome; Vitamin B Complex

Topics: Aging; Child; Dementia; Electroencephalography; Female; Homocystinuria; Humans; Hydroxocobalamin; Leucovorin; Magnetic Resonance Imaging; Metabolism, Inborn Errors; Methylmalonic Acid; Vitamin B 12

Granulocytes from a 6-year-old boy with congenital transcobalamin II (TC II) deficiency were found to have abnormally low antibacterial activity against Staphylococcus aureus and very low intracellular levels of the cobalamin coenzymes. Transfusion of hydroxocobalamin (OH-Cbl) bound to normal plasma temporarily restored granulocyte bactericidal activity and increased cellular levels of the cobalamin coenzymes. Granulocyte function was also temporarily restored by oral Leucovorin. The defect appeared to be causally related to the patient's TC II deficiency and indirectly to a deficiency of cobalamin and folate coenzymes.

Topics: Blood Proteins; Blood Transfusion; Child; Granulocytes; Humans; Hydroxocobalamin; Leucovorin; Male; Metabolism, Inborn Errors; Phagocyte Bactericidal Dysfunction; Transcobalamins

Topics: Administration, Oral; Anemia, Macrocytic; Child; Consanguinity; Female; Folic Acid; Folic Acid Deficiency; Humans; Injections, Intramuscular; Intestinal Absorption; Leucovorin; Metabolism, Inborn Errors; Recurrence; Stomatitis; Vitamin B 12; Yeast, Dried

Topics: Animals; Cattle; Chemical Phenomena; Chemistry; Folic Acid; Leucovorin; Ligases; Lyases; Metabolism, Inborn Errors; Tetrahydrofolate Dehydrogenase