title: Plasma alpha-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 alpha-ketoglutarate concentration ([alpha-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 58 microM. However, this hyperammonemia was preceded by a fall in plasma [alpha-KG] to 15 microM 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 [alpha-KG] became subnormal (14 microM) 8 days before the rise in plasma ammonium concentration [NH4+] (52 microM) and 14 days before the onset of hyperammonemic coma. In eight patients with urea cycle enzymopathies, there was a highly significant (P less than 0.01) negative linear correlation between [NH4+] and [alpha-KG]. In patients with portal-systemic encephalopathy, there was a similar relationship between [NH4+] and [alpha-KG], although the absolute [alpha-KG] levels in these patients were normal (23 +/- 4 microM) while the patients were hyperammonemic (88 +/- 25 microM).
mesh_terms: D000293:Adolescent; D000328:Adult; D000592:Amino Acid Metabolism, Inborn Errors / Q000097:blood*; D000641:Ammonia / Q000097:blood*; D001124:Argininosuccinate Synthase / Q000172:deficiency*; D001125:Argininosuccinic Acid; D056807:Argininosuccinic Aciduria; D002222:Carbamoyl-Phosphate Synthase (Ammonia) / Q000172:deficiency*; D002221:Carbamyl Phosphate; D002648:Child; D002675:Child, Preschool; D003128:Coma / Q000097:blood / Q000209:etiology*; D005260:Female; D006501:Hepatic Encephalopathy / Q000097:blood; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007656:Ketoglutaric Acids / Q000097:blood*; D008025:Ligases / Q000172:deficiency*; D008190:Lyases / Q000172:deficiency*; D008297:Male; D008875:Middle Aged; D009952:Ornithine; D020163:Ornithine Carbamoyltransferase Deficiency Disease
chemical_list: D007656:Ketoglutaric Acids; D001125:Argininosuccinic Acid; D002221:Carbamyl Phosphate; D000641:Ammonia; D009952:Ornithine; D008190:Lyases; D008025:Ligases; D002222:Carbamoyl-Phosphate Synthase (Ammonia); D001124:Argininosuccinate Synthase