Tiglylglycine excreted in urine in disorders of isoleucine metabolism and the respiratory chain measured by stable isotope dilution GC-MS

Clin Chem. 1994 Oct;40(10):1879-83.


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.

MeSH terms

  • Acetyl-CoA C-Acyltransferase / deficiency
  • Adolescent
  • Amino Acid Metabolism, Inborn Errors / urine*
  • Child
  • Child, Preschool
  • Electron Transport*
  • Gas Chromatography-Mass Spectrometry / methods*
  • Gas Chromatography-Mass Spectrometry / statistics & numerical data
  • Glycine / analogs & derivatives*
  • Glycine / urine
  • Humans
  • Infant
  • Infant, Newborn
  • Isoleucine / metabolism*


  • Isoleucine
  • tiglylglycine
  • Acetyl-CoA C-Acyltransferase
  • Glycine