All issues > Volume 47(10); 2004

Original Article

Korean J Pediatr. 2004;47(10):1047-1052. Published online October 15, 2004.

Quantification of Organic Acids in Amniotic Fluid for Prenatal Diagnosis of Organic Acidemia

Chang Bum CB Koh¹, Dong Soo DS Shin¹, Eun Joo EJ Bae¹, Won Il WI Park¹, Kyeung Ja KJ Lee¹, Hong Jin HJ Lee¹, Young Y Jo², Seung Won SW Lee², Ui Sun US Noh²

¹Department of Pediatrics, College of Medicine, Hallym University, Chuncheon, Korea
²Department of Obstetrics and Gynecology,College of Medicine, Hallym University, Chuncheon, Korea

Correspondence Hong Jin HJ Lee ,Email: hongjlee@hallym.ac.kr

Abstract

Purpose
: Since 1997, the quantification of organic acids in urine has become possible in Korea. This helped to diagnose a great variety of inborn errors of metabolism. However, we still don't know the normal value of organic acids in amniotic fluid, therefore it is impossible for doctors to make a correct diagnosis of inborn errors of metabolism in prenatal care. We tried to confirm the normal value of organic acid in amniotic fluid.
Methods
: From Jan. 1998 to Dec. 2001, we carried out amniocentesis and were able to obtain 43 samples of amniotic fluid from between 16 and 20 weeks of gestation, and quantified 82 organic acids to come up with a normal value. Organic acid concentrations were quantified with gas chromatography, and the individual acids were identified with mass spectrometry. To isolate organic acids from amniotic fluid, we used a solvent extraction method with ethylacetate. Derivatization was done with MSTFA(N-methy-N-trimethylsilylfluoroacetamide).
Results
: The results of this study showed that when organic acid concentrations in amniotic fluid were compared with those in urine, TCA cycle intermediates(lactate, pyruvate, malate, 2-ketoglutarate, citrate etc) and ketone body(3-hydroxybutyric acid, acetoacetate etc) were found at significantly higher levels.
Conclusion
: Because TCA cycle intermediate in amniotic fluid is found at high concentrations, we could expect that diagnosis of mitochondria disorder is difficult. Organic acids other than TCA cycle intermediates were undetectable in amniotic fluid. Therefore, prenatal diagnosis of organic acidemias is possible. In our study, the prenatal diagnosis of methylmalonic acidemia could be made by using the measurement of methylmalonic acid in the amniotic fluid taken at high risk pregnancy with a family history of methylmalonic acidemia.

Keywords :Amniotic fluid, Prenatal diagnosis, Organic aciduria, Methylmalonic acidemia