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

Abstract

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.

• Authors: Y Inoue, T Kuhara
• Journal: Journal of chromatography. B, Analytical technologies in the biomedical and life sciences (J Chromatogr B Analyt Technol Biomed Life Sci) Vol. 776 Issue 1 Pg. 71-7 (Aug 25 2002) ISSN: 1570-0232 [Print] Netherlands
• PMID: 12127327 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2002 Elsevier Science B.V.

Chemical References

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

Topics

• 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)