Plasma α-ketoglutarate in urea cycle enzymopathies and its role as a harbinger of hyperammonemic coma

Abstract

Metabolic observations during early stages of hyperammonemia in two infants with ornithine transcarbamylase deficiency suggest that plasma a-ketoglutarate concentration ([α-KG]) becomes subnormal before the development of hyperammonemic coma. In one case, plasma [NH4+] remained normal until 40 days of age when it rose to 57 μM. However, this hyperammonemia was preceded by a fall in plasma [α-KG] to 15 μM at 27 days of age. It was only after severe hyperammonemia was established at 50 days of age that coma supervened. In the second case, plasma [α-KG] became subnormal (14 μM) 8 days before the rise in plasma ammonium concentration [NF4+] (52 μM) and 14 days before the onset of hyperammonemic coma. In eight patients with urea cycle enzymopathies, there was a highly significant (P < 0.01) negative linear correlation between [NF4+] and [α-KG]. In patients with portal- systemic encephalopathy, there was a similar relationship between [NH4+] and [α-KG], although the absolute [α-KG] levels in these patients were normal (23 ± 4 μM) while the patients were hyperammonemic (88 ± 25 μM). Speculation: The inverse linear correlation between (α-KG) and [NF4+] levels in patients with urea cycle enzymopathies suggest that plasma (α-KG) may presage hyperammonemic coma. However, the different (α-KG) levels in patients with cirrhosis and portal- systemic shunting imply different pathophysiologic mechanisms for hyperammonemic coma as compared to hepatic coma. © 1980 International Pediatric Research Foundation, Inc.