Rapid and sensitive method for prenatal diagnosis of propionic acidemia using stable isotope dilution gas chromatography-mass spectrometry and urease pretreatment

J Chromatogr B Analyt Technol Biomed Life Sci. 2002 Aug 25;776(1):71-7. doi: 10.1016/s1570-0232(02)00076-4.


Propionic acidemia is one of the most frequent inborn errors of metabolism caused by a deficiency of propionyl-CoA carboxylase. Methylcitric acid, a key indicator of this disorder, is increased in amniotic fluid when a fetus is affected. Therefore, the direct chemical analysis of cell-free amniotic fluid for methylcitric acid, using stable isotope dilution gas chromatography-mass spectrometry, was carried out for the prenatal diagnosis of propionic acidemia. We developed a simple, highly sensitive, and accurate method for quantitation of this polar methylcitric acid in amniotic fluids by applying a simplified urease pretreatment which we devised earlier for urine. As the recovery of methylcitric acid from amniotic fluid was as high as 91% with a coefficient of variation lower than 3% in this procedure, only 0.02 ml of sample was required for the analysis of the affected fetus. This new procedure takes 1 h for sample pretreatment, including derivatization, and 15 min for GC-MS measurement and provides final results within 1.5 h.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amniotic Fluid / metabolism
  • Citric Acid / metabolism
  • Female
  • Gas Chromatography-Mass Spectrometry / methods*
  • Humans
  • Isotopes
  • Metabolism, Inborn Errors / diagnosis*
  • Pregnancy
  • Prenatal Diagnosis / methods*
  • Propionates / blood*
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Urease / metabolism*


  • Isotopes
  • Propionates
  • Citric Acid
  • Urease
  • propionic acid