dextromethorphan and Metabolism--Inborn-Errors

We report a five-year-old boy with 4-hydroxybutyric aciduria. The child presented with global developmental delay, severe hypotonia and myoclonic seizures. The urine 4-hydroxybutyric acid was 1038 times that of normal, and other organic acids related to its further metabolism were also increased. Electroencephalography showed findings indicative of cerebral dysfunction. However, other neurophysiological studies were normal. Clinical improvement was observed after the administration of vigabatrin and dextromethorphan. Magnetic resonance imaging of the brain revealed cerebellar vermin atrophy and subtle white matter changes in the cerebral hemispheres. Fluorine-18 labeled 2-fluoro-2-deoxyglucose positron emission tomographic (FDG PET) scan of the brain showed a marked decrease in the cerebellar metabolism, probably related to atrophy of cerebellar vermis and secondary cerebellar deafferentation. FDG PET scan is found to be of value in the understanding and assessment of brain functional alterations. It may be useful in monitoring and optimizing treatment strategies of this rare disease.

Topics: Brain; Child, Preschool; Dextromethorphan; Fluorodeoxyglucose F18; Humans; Hydroxybutyrates; Magnetic Resonance Imaging; Male; Metabolism, Inborn Errors; Saudi Arabia; Tomography, Emission-Computed; Vigabatrin

Topics: Dextromethorphan; Enzyme Inhibitors; Excitatory Amino Acid Antagonists; Female; Food Preservatives; gamma-Aminobutyric Acid; Glycine; Humans; Infant, Newborn; Male; Metabolism, Inborn Errors; Sodium Benzoate; Vigabatrin

Topics: Anticonvulsants; Child, Preschool; Coenzymes; Dextromethorphan; Epilepsy; Humans; Male; Metabolism, Inborn Errors; Metalloproteins; Molybdenum Cofactors; N-Methylaspartate; Pteridines

The clinical findings in six patients from three families with 4-hydroxybutyric aciduria are described. The onset of disease was in early infancy in all cases. All infants presented with severe global delay and severe hypotonia, and all patients had seizure disorder. Eye findings included optic atrophy in two patients, and retinitis pigmentosa in one. Three patients had choreoathetosis, two had myoclonus and one had severe dystonia. The urine 4-hydroxybutyric acid was 300-1000 times that of normal, and other organic acids related to its further metabolism or to its inhibitory effect on beta-oxidation were also increased. The administration of vigabatrine rapidly reduced the excretion of 4-hydroxybutyric acid promptly, and in the long-term its excretion could be kept at 80-200 times that of normal. However, the clinical course of the disease improved in only two, remained the same in two, and worsened in the remaining two patients.

Topics: Adult; Anticonvulsants; Brain; Child; Child, Preschool; Dextromethorphan; Female; gamma-Aminobutyric Acid; Humans; Hydroxybutyrates; Infant; Magnetic Resonance Imaging; Male; Metabolism, Inborn Errors; Nervous System Diseases; Seizures; Vigabatrin

To test the hypothesis that nonketotic hyperglycinemia causes overstimulation of the excitatory N-methyl-D-aspartate receptor by allosteric glycine activation, and that reduction of glycine and blocking of the cation channel coupled to the receptor would be beneficial, we administered benzoate and dextromethorphan, a blocker of the N-methyl-D-aspartate channel to an infant with nonketotic hyperglycinemia. Therapy with benzoate, 500 mg/kg per day, was started on day 5, and the dosage was increased to 750 mg/kg per day on day 8, with prompt normalization of the neurologic and electroencephalographic findings. The glycine concentrations in both plasma and cerebrospinal fluid were substantially reduced. Dextromethorphan was added to the regimen on day 12. The electroencephalogram remained normal until the infant was 8 months of age, when diffuse slowing became apparent. Serial brain magnetic resonance imaging showed delayed myelination. At 12 months of age, physical examination findings and growth were normal except for hypotonia. The developmental quotient was approximately 60, and the child was free of seizures. This outcome, although not ideal, is better than that typical for nonketotic hyperglycinemia. Our results suggest that trials with additional patients and other N-methyl-D-aspartate cation channel blockers are warranted.

Topics: Benzoates; Benzoic Acid; Dextromethorphan; Electroencephalography; Glycine; Humans; Infant; Infant, Newborn; Ketosis; Male; Metabolism, Inborn Errors; Neurologic Examination; Receptors, N-Methyl-D-Aspartate