sodium-benzoate and Epilepsy

To evaluate the impact of sodium benzoate and dextromethorphan treatment on patients with the attenuated form of nonketotic hyperglycinemia.. Families were recruited with 2 siblings both affected with attenuated nonketotic hyperglycinemia. Genetic mutations were expressed to identify residual activity. The outcome on developmental progress and seizures was compared between the first child diagnosed and treated late with the second child diagnosed at birth and treated aggressively from the newborn period using dextromethorphan and benzoate at dosing sufficient to normalize plasma glycine levels. Both siblings were evaluated with similar standardized neurodevelopmental measures.. In each sibling set, the second sibling treated from the neonatal period achieved earlier and more developmental milestones, and had a higher developmental quotient. In 3 of the 4 sibling pairs, the younger sibling had no seizures whereas the first child had a seizure disorder. The adaptive behavior subdomains of socialization and daily living skills improved more than motor skills and communication.. Early treatment with dextromethorphan and sodium benzoate sufficient to normalize plasma glycine levels is effective at improving outcome if used in children with attenuated disease with mutations providing residual activity and when started from the neonatal period.

Topics: Child; Child Development; Child, Preschool; Colorado; Delayed Diagnosis; Dextromethorphan; Early Diagnosis; Epilepsy; Excitatory Amino Acid Antagonists; Female; Humans; Hyperglycinemia, Nonketotic; Infant; Infant, Newborn; Intelligence Tests; Male; Neuropsychological Tests; Siblings; Sodium Benzoate; Time-to-Treatment

In areas without expanded newborn screening, instead of presenting neonatally, patients with arginase deficiency typically present with spastic paraplegia in early childhood. Diagnosis of this rare neurometabolic disease poses the first challenge because it is often misdiagnosed as cerebral palsy during initial stages. We describe arginase deficiency in a 20-year-old woman with spastic paraplegia, progressive dystonia, dementia, peripheral neuropathy, epilepsy, liver cirrhosis, and non-B/non-C hepatocellular carcinoma. A novel homozygous mutation NM_000045.2 (ARG1):c.673del (p.Arg225GlyfsX5) was detected. We suggest that all children presenting with progressive neurodegeneration or spastic paraplegia in the absence of risk factors for cerebral palsy should be screened for inborn errors of metabolism, including arginase deficiency. For monitoring urea cycle defects, noninvasive imaging screening for liver fibrosis and hepatocellular carcinoma can help ensure early detection, with potential treatment implications.

Topics: Anticonvulsants; Arginase; Base Sequence; Carcinoma, Hepatocellular; Cerebral Palsy; Codon, Nonsense; Combined Modality Therapy; Contraindications; Delayed Diagnosis; Dementia; Diagnostic Errors; Disease Progression; Epilepsy; Fatal Outcome; Female; Humans; Hyperargininemia; Liver; Liver Cirrhosis; Liver Neoplasms; Molecular Sequence Data; Palliative Care; Phenotype; Radiography; Sequence Deletion; Sodium Benzoate; Ultrasonography; Valproic Acid; Young Adult

Topics: Adult; Anesthesia, General; Epilepsy; Fasting; Female; Humans; Hyperammonemia; Intellectual Disability; Oral Surgical Procedures; Ornithine Carbamoyltransferase Deficiency Disease; Postoperative Complications; Preoperative Care; Proteins; Sodium Benzoate; Substance Withdrawal Syndrome; Urea