EFFICACY OF LOW-DOSE DEXTROMETHORPHAN IN THE TREATMENT OF NONKETOTIC HYPERGLYCINEMIA

Nonketotic hyperglycinemia (NKH) is an inborn error of glycine degrada tion causing muscular hypotonia, seizures, apnea, and lethargy; it has a poor prognosis. Accumulation of glycine in the brain is thought to cause excessive stimulation of the N-methyl-D-aspartate receptor. Dext romethorphan (DM), an N-methyl-D-aspartate receptor antagonist, in dos es of 5 to 35 mg/kg per day has been shown to have beneficial therapeu tic effects in some patients with NKH. We report the case of a 1-year- old infant with NKH, seizure disorder, and psychomotor delay who was c linically seizure free during treatment with sodium benzoate, arginine , benzodiazepam, and phenobarbital. Although sodium benzoate normalize d serum glycine levels (103 to 125 mu mol/L), cerebrospinal fluid glyc ine levels remained elevated (42 to 47 mu mol/L), with epileptiform ac tivity on electroencephalography. The addition of low-dose DM (0.25 mg /kg per day) to the treatment led to improvement of electroencephalogr aphic activity, resolution of nystagmus with increased eye contact, an d modest progression of developmental milestones. These data suggest t hat DM at doses significantly lower than previously reported may be be neficial in some patients with NKH. Treatment with low-dose DM needs f urther evaluation.