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Molecular and Cellular Biochemistry

, Volume 359, Issue 1–2, pp 205–216 | Cite as

Metabolic profile of amniotic fluid as a biochemical tool to screen for inborn errors of metabolism and fetal anomalies

  • Angela M. Amorini
  • Claudio Giorlandino
  • Salvatore Longo
  • Serafina D’Urso
  • Alvaro Mesoraca
  • Maria Luisa Santoro
  • Marika Picardi
  • Stefano Gullotta
  • Pietro Cignini
  • Dario Lazzarino
  • Giuseppe Lazzarino
  • Barbara Tavazzi
Article

Abstract

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 In this study, we initially assayed purines, pyrimidines, and amino compounds in 1,257 AF withdrawn between the 15th and the 20th week of gestation from actually normal pregnancies (normal gestations, normal offspring).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.

Keywords

Amniotic fluid Purines Pyrimidines Amino acids Prenatal screening Inborn errors of metabolism 

Abbreviations

Ala

Alanine

AAAA

α-aminoadipic acid

AF

Amniotic fluid

Arg

Arginine

Arg-succ

Argininosuccinate

Asn

Asparagine

Asp

Aspartate

Carn

Carnosine

CI

Confidence interval

Cit

Citrulline

CV

Coefficient of variation

Cystat

l-Cystathionine

GABA

γ-Aminobutyrate

Gln

Glutamine

Glu

Glutamate

Gly

Glycine

HPLC

High-performance liquid chromatography

His

Histidine

IEM

Inborn errors of metabolism

Ile

Isoleucine

ISTD

Internal standard

Leu

Leucine

LOD

Lowest limit of detection

LOQ

Lowest limit of quantification

Lys

Lysine

MA

Malonic acid

Met

Methionine

MHPA

Mild hyperphenylalaninemia

MMA

Methylmalonic acid

MPA

3-Mercaptopropionic acid

NAA

N-acetylaspartate

Norval

Norvaline

OPA

Ortophtalaldehyde

Orn

Ornithine

PAH

Phenylalanine hydroxylase

Phe

Phenylalanine

PKU

Phenylketonuria

SAH

S-adenosylhomocysteine

SAM

S-adenosylmethionine

Ser

Serine

Tau

Taurine

Thr

Threonine

Trp

Tryptophane

Tyr

Tyrosine

Val

Valine

Notes

Acknowledgments

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.

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Copyright information

© Springer Science+Business Media, LLC. 2011

Authors and Affiliations

  • Angela M. Amorini
    • 1
  • Claudio Giorlandino
    • 2
  • Salvatore Longo
    • 3
  • Serafina D’Urso
    • 1
  • Alvaro Mesoraca
    • 2
  • Maria Luisa Santoro
    • 2
  • Marika Picardi
    • 1
  • Stefano Gullotta
    • 3
  • Pietro Cignini
    • 2
  • Dario Lazzarino
    • 3
  • Giuseppe Lazzarino
    • 3
  • Barbara Tavazzi
    • 1
  1. 1.Institute of Biochemistry and Clinical BiochemistryCatholic University of Rome “Sacro Cuore”RomeItaly
  2. 2.Department of Prenatal DiagnosisArtemisia Fetal-Maternal Medical CentreRomeItaly
  3. 3.Department of Biology, Geology and Environmental Sciences, Division of Biochemistry and Molecular BiologyUniversity of CataniaCataniaItaly

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