Propionyl-CoA carboxylase deficiency with overflow of metabolites of isoleucine catabolism at all levels.
An 11-year old girl with spastic paraplegia and mental retardation has suffered from attacks of metabolic acidosis since the age of 18 months. "Ketotic hyperglycinemia" was diagnosed when she was 3 years old. Reinvestigation at 9 1/2 years included a two-day load with L-isoleucine, and propionyl-CoA carboxylase assay in cultured fibroblasts. The following compounds increased following the load: 3-hydroxypropionic acid, 2-methyl-3-hydroxybutyric acid, 2-ethylhydracrylic acid, 3-hydroxy-n-valeric acid, 3-oxo-n-valeric acid, 2-methyl-3-oxobutyric acid, 2-oxo-3-methylvaleric acid, 2-methyl-3-oxovaleric acid, N-tiglylglycine, methylcitric acid and butanone. Small amounts of alloisoleucine appeared in plasma. Propionyl-CoA carboxylase deficiency was suggested by this metabolite pattern and demonstrated in cultured fibroblasts.
D000138:Acidosis / Q000209:etiology; D000592:Amino Acid Metabolism, Inborn Errors / Q000150:complications / Q000175:diagnosis*; D002262:Carboxy-Lyases / Q000032:analysis / Q000172:deficiency*; D002648:Child; D005260:Female; D005347:Fibroblasts / Q000201:enzymology; D006801:Humans; D008607:Intellectual Disability / Q000209:etiology; D007532:Isoleucine / Q000378:metabolism*; D009128:Muscle Spasticity; D010264:Paraplegia / Q000209:etiology
D007532:Isoleucine; D002262:Carboxy-Lyases