Treatment of neonatal onset Non-Ketotic Hyperglycinemia with combined Sodium Benzoate and Dextromethorphan regimen. M.Y. Hasan¹, M. Velinov^{2, 3}, V. Agarwalla¹, G. Kupchik². 1) Pediatrics, Brookdale University Hospital and Medical Center, Brooklyn, NY; 2) Maimonides Medical Center, Brooklyn, NY; 3) NYS Institute for Basic Research, Staten Island, NY.
   Non-Ketotic Hyperglycinemia (NKHG) is an inborn error of metabolism, due to defect in the glycine cleavage system, with excessive accumulation of glycine in the plasma and central nervous system (CNS).It presents with progressive encephalopathy, seizures and hypotonia. Different approaches for the treatment of this condition were previously suggested including low protein intake, administration of Sodium Benzoate, Dextromethorphan, and Imipramine. Finally, dialysis was used in severe cases. We report on a male infant with severe neonatal type of NKHG, who presented at 6 days of age with acute encephalopathy, hypoglycemia, severe dehydration, and respiratory failure. On admission his urinary glycine level was 40989 mmols/l, at 11 days of age his CSF glycine was found to be 264 mmols/l, and plasma glycine 1162mmols/l, with CSF/plasma glycine ratio of 0.23. After establishing the diagnosis of NKHG, treatment was started with the combination of Sodium Benzoate 500mg/kg/day, and Dextromethorphan 5mg/kg/day. The response to this therapeutic regimen was very good. After about 10 days of therapy it became possible to discontinue the respiratory support. 3 weeks after initiation of treatment it became possible to manage this condition on an outpatient basis. At the discharge, glycine levels were 102 and 86 mmols/l in plasma and CSF respectively, with a ratio of 0.84. Sodium Benzoate is used because of its action in reducing the glycine levels in body fluids. Dextromethorphan acts by blocking the NMDA receptors in the brain (Hamosh A - J Pediatr - 1998 Apr; 132(4): 709-13). Our regimen proved to be very effective in counteracting the acute effects of elevated glycine concentration in CNS. Such treatment may be lifesaving in cases of severe neonatal forms of NKHG. Long term follow up with patient is needed in order to assess the consequences for growth and development of this therapeutic approach.