Tiglylglycine excreted in urine in disorders of isoleucine metabolism and the respiratory chain measured by stable isotope dilution GC-MS.
Tiglyglycine (TG), an intermediate product of the catabolism of isoleucine, is increased in the urine of patients with beta-ketothiolase deficiency or with disorders of propionate metabolism. It is also implicated as a useful diagnostic marker in disorders of the respiratory chain. We present a method for the synthesis of TG and tiglyl[13C, 15N]glycine and the development of a stable isotope dilution mass spectrometric assay for TG. We compare data from controls with that from subjects with beta-ketothiolase deficiency and propionyl-CoA carboxylase deficiency, and with six patients with enzyme-confirmed disorders of the respiratory chain. TG was increased in the urine from all of the patient groups. The increased TG excretion did not persist in one patient with a respiratory chain defect, which suggests that, in some patients, multiple sample analysis may be necessary to identify a respiratory chain defect. This is the first urinary compound to be implicated as a potential marker of disorders of the respiratory chain.
Bennett
M J
MJ
Department of Pathology, Children's Medical Center of Dallas, University of Texas Southwestern Medical Center 75235.
Powell
S
S
Swartling
D J
DJ
Gibson
K M
KM
D000102:Acetyl-CoA C-Acyltransferase / Q000172:deficiency; D000293:Adolescent; D000592:Amino Acid Metabolism, Inborn Errors / Q000652:urine*; D002648:Child; D002675:Child, Preschool; D004579:Electron Transport; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods* / Q000706:statistics & numerical data; D005998:Glycine / Q000031:analogs & derivatives* / Q000652:urine; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007532:Isoleucine / Q000378:metabolism*
D007532:Isoleucine; C003603:tiglylglycine; D000102:Acetyl-CoA C-Acyltransferase; D005998:Glycine