Urinary excretion of 2-methylacetoacetate, 2-methyl-3-hydroxybutyrate and tiglylglycine after isoleucine loading in the diagnosis of 2-methylacetoacetyl-CoA thiolase deficiency.
The concentrations of 2-methylacetoacetate, 2-methyl-3-hydroxybutyrate and tiglylglycine were determined by gas chromatography-mass spectrometry in urine collected before and for 8 h after loading with 100 mg of isoleucine per kg of body weight. The sum of 2-methylacetoacetate and 2-butanone, a decarboxylation product, was determined as the 2-butanone dinitrophenylhydrazone derivative. Substantial increases in each compound were encountered in a patient with a documented defect of 2-methylacetoacetyl-CoA thiolase. Increased quantities of 2-methyl-3-hydroxybutyrate and tiglylglycine were also found in four children with clinical symptoms similar to those associated with 2-methylacetoacetyl-CoA thiolase deficiency but in whom the activity of the enzyme was found to be normal. The concentration of 2-methylacetoacetate plus 2-butanone in the urine increased after an isoleucine load only in the patient with 2-methylacetoacetyl-CoA thiolase deficiency.
Aramaki
S
S
Department of Pediatrics, University of California San Diego, La Jolla 92093.
Lehotay
D
D
Sweetman
L
L
Nyhan
W L
WL
Winter
S C
SC
Middleton
B
B
D000090:Acetoacetates / Q000652:urine*; D000102:Acetyl-CoA C-Acyltransferase / Q000172:deficiency*; D002074:Butanones / Q000652:urine; D005998:Glycine / Q000031:analogs & derivatives* / Q000652:urine; D006801:Humans; D006885:Hydroxybutyrates / Q000652:urine*; D007223:Infant; D007532:Isoleucine; D008297:Male
D000090:Acetoacetates; D002074:Butanones; D006885:Hydroxybutyrates; D007532:Isoleucine; C003603:tiglylglycine; C016579:2-methyl-3-hydroxybutyric acid; C005222:methylethyl ketone; C005217:methyl acetoacetate; D000102:Acetyl-CoA C-Acyltransferase; D005998:Glycine