LONG-TERM USE OF HIGH-DOSE BENZOATE AND DEXTROMETHORPHAN FOR THE TREATMENT OF NONKETOTIC HYPERGLYCINEMIA

Objective: The objective of this study was to test the hypotheses that reduction of glycine and blocking of the N-methyl-D-aspartate recepto r channel complex would be beneficial for both seizure reduction and d evelopmental progress in patients with nonketotic hyperglycinemia. Met hods: We administered benzoate (at doses of 500 to 750 mg/kg/day) and dextromethorphan (at doses of 3.5 to 22.5 mg/kg/day) to four infants w ith nonketotic hyperglycinemia with follow-up of 3 months to 6 years. Results: Benzoate reduced to normal the glycine concentration in plasm a and substantially reduced but did not normalize the glycine concentr ation in cerebrospinal fluid. Dextromethorphan was a potent anticonvul sant in some but not all patients. There was remarkable interpatient v ariability in dextromethorphan metabolism. Three patients are living ( ages ranging from 4 to 6 years) and are moderately to severely develop mentally delayed; two are free of seizures. The third patient, with th e slowest development, had intractable seizures for nearly a month bef ore diagnosis, and although seizure-free for 30 months, now has grand- mal seizures. One patient died of intractable seizures at 3 months. Co nclusions: These outcomes suggest that benzoate and dextromethorphan a re not uniformly effective in nonketotic hyperglycinemia, but for some patients they improve arousal, decrease or eliminate seizures, and al low for some developmental progress. Trials with additional patients a nd other receptor channel blockers are warranted.