QUINOLINIC ACID IN CHILDREN WITH CONGENITAL HYPERAMMONEMIA

Levels of the excitotoxin quinolinic acid (QUIN) were measured in the cerebrospinal fluid of infants and children with congenital hyperammon emia. Twofold to tenfold elevations of QUIN were found in 4 neonates i n hyperammonemic coma (QUIN range, 250-990 nM; control mean, 110 +/- 9 0 nM; p < 0.005). Similar elevations of neopterin were found (range, 2 4-75 nM; control mean, 9.0 +/- 4.9 nM; p < 0.005). In addition, signif icant elevations of QUIN were found in 14 older children with congenit al hyperammonemia (mean, 50 +/- 20 vs 17 +/- 6 nM; p < 0.05). Neopteri n levels were not elevated in these children. The QUIN may originate f rom an increase in tryptophan transport across the blood-brain barrier or from induction of indolamine-2,3-dioxygenase activity. These findi ngs support a role for QUIN in the neuropathology of congenital hypera mmonemia. They also suggest the potential utility of N-methyl-D-aspart ate receptor-blocking agents or inhibitors of QUIN synthesis in the tr eatment of hyperammonemic coma.