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

Koh, Chang Bum; Shin, Dong Soo; Bae, Eun Joo; Park, Won Il; Lee, Kyeung Ja; Lee, Hong Jin; Jo, Young; Lee, Seung Won; Noh, Ui Sun

Original Article

Korean Journal of Pediatrics 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 Koh¹, Dong Soo Shin¹, Eun Joo Bae¹, Won Il Park¹, Kyeung Ja Lee¹, Hong Jin Lee¹, Young Jo², Seung Won Lee², Ui Sun Noh²

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

유기산혈증의 산전진단을 위한 양수내 유기산의 정량분석

고창범^¹^, 신동수^¹^, 배은주^¹^, 박원일^¹^, 이경자^¹^, 이홍진^¹^, 조용^²^, 이성원^²^, 노의선^²

^¹한림대학교 의과대학 소아과학교실
^²한림대학교 의과대학 산부인과학교실

Correspondence:
Hong Jin 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.

Key Words: Amniotic fluid, Prenatal diagnosis, Organic aciduria, Methylmalonic acidemia