A patient with glycine encephalopathy may be treated with both benzoate and dextromethorphan. The glycine and glycine-serine indices are measures of endogenous glycine excess. It is assumed that the difference between glycine endogenous synthesis and glycine endogenous use expressed in terms of body weight are relatively constant in children over 1 year of age.
Benzoate forms a coenzyme A ester which conjugates with glycine to form hippurate which can be excreted in the urine, thereby eliminating glycine. High doses of benzoate may be associated with toxicity such as gastric irritation that limits therapy. Dextromethorphan blocks the NMDA (N-methyl-D-aspartic acid) receptor which may be activated by glycine.
Parameters:
(1) daily dose of benzoate needed to normalize plasma glycine concentrations in mmol
(2) glycine content of food in mmol per day
(3) serine content of food in mmol per day
(4) body weight in kilograms
glycine index =
= ((benzoate dose) - (glycine in food)) / (body weight)
glycine-serine index =
= ((benzoate dose) - (glycine in food) - (serine in food)) / (body weight)
Interpretation:
• A glycine index > 3 mmol/kg per day was associated with severe glycine encephalopathy.
• A glycine-serine index > 2.5 mmol/kg per day was associated with severe glycine encephalopathy.
• A glycine index < 2 mmol/kg per day is associated with mild disease.
• The glycine index tends to be stable for a patient over time.
