Metabolic profile of amniotic fluid as a biochemical tool to screen for inborn errors of metabolism and fetal anomalies
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Physiologic concentration in amniotic fluid (AF) of several metabolites has not been established with certainty. In this study, we initially assayed purines, pyrimidines, and amino compounds in 1,257 AF withdrawn between the 15th and the 20th week of gestation from actually normal pregnancies (normal gestations, normal offspring). Results allowed to determine physiologic reference intervals for 45 compounds. In these AF, not all purines and pyrimidines were detectable and uric acid (238.35 ± 76.31 μmol/l) had the highest concentration. All amino compounds were measurable, with alanine having the highest concentration (401.10 ± 88.47 μmol/l). In the second part of the study, we performed a blind metabolic screening of AF to evaluate the utility of this biochemical analysis as an additional test in amniocenteses. In 1,295 additional AF from normal pregnancies, all metabolites fell within the confidence intervals determined in the first part of the study. In 24 additional AF from women carrying Down’s syndrome-affected fetuses, glutamate, glutamine, glycine, taurine, valine, isoleucine, leucine, ornithine, and lysine were different from physiologic reference values. One AF sample showed phenylalanine level of 375.54 μmol/l (mean value in normal AF = 65.07 μmol/l) and was from a woman with unreported phenylketonuria with mild hyperphenylalaninemia (serum phenylalanine = 360.88 μmol/l), carrying the IVS 4 + 5 G-T and D394A mutations. The fetus was heterozygote for the maternal D394A mutation. An appropriate diet maintained the mother phenylalanine in the range of normality during pregnancy, avoiding serious damage in fetal and neonatal development. These results suggest that the metabolic screening of AF might be considered as an additional biochemical test in amniocenteses useful to highlight anomalies potentially related to IEM.
KeywordsAmniotic fluid Purines Pyrimidines Amino acids Prenatal screening Inborn errors of metabolism
Coefficient of variation
High-performance liquid chromatography
Inborn errors of metabolism
Lowest limit of detection
Lowest limit of quantification
This study was supported in part by research funds of the University of Catania. A special thank to Dr. Roberto Tozzi for his significant contribution in the statistical analysis of data.
- 14.Tavazzi B, Lazzarino G, Leone P, Amorini AM, Bellia F, Janson CG, Di Pietro V, Ceccarelli L, Donzelli S, Francis JS, Giardina B (2005) Simultaneous high performance liquid chromatographic separation of purines, pyrimidines, N-acetylated amino acids, and dicarboxylic acids for the chemical diagnosis of inborn errors of metabolism. Clin Biochem 38:997–1008PubMedCrossRefGoogle Scholar
- 17.Waterval WA, Scheijen JL, Ortmans-Ploemen MM, Habets-van der Poel CD, Bierau J (2009) Quantitative UPLC-MS/MS analysis of underivatised amino acids in body fluids is a reliable tool for the diagnosis and follow-up of patients with inborn errors of metabolism. Clin Chim Acta 407:35–42CrossRefGoogle Scholar
- 26.Graca G, Duarte IF, Barros AS, Goodfellow BJ, Diaz SO, Pinto J, Carreira IM, Galhano E, Pita C, Gil AM (2010) The impact of prenatal disorders on the metabolic profile of 2nd trimester amniotic fluid: a nuclear magnetic resonance (NMR) metabonomic study. J Proteome Res 9:6016–6024PubMedCrossRefGoogle Scholar