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

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 In this study, we initially assayed purines, pyrimidines, and amino compounds in 1,257 AF withdrawn between the 15th and the 20th week of gestation from actually normal pregnancies (normal gestations, normal offspring).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

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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

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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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Authors and Affiliations

  1. Institute of Biochemistry and Clinical Biochemistry, Catholic University of Rome “Sacro Cuore”, Largo F. Vito 1, 00164, Rome, Italy

    Angela M. Amorini, Serafina D’Urso, Marika Picardi & Barbara Tavazzi

  2. Department of Prenatal Diagnosis, Artemisia Fetal-Maternal Medical Centre, Viale Liegi 45, 00198, Rome, Italy

    Claudio Giorlandino, Alvaro Mesoraca, Maria Luisa Santoro & Pietro Cignini

  3. Department of Biology, Geology and Environmental Sciences, Division of Biochemistry and Molecular Biology, University of Catania, Building 2, III Floor, Viale A. Doria 6, 95125, Catania, Italy

    Salvatore Longo, Stefano Gullotta, Dario Lazzarino & Giuseppe Lazzarino

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  1. Angela M. Amorini
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  2. Claudio Giorlandino
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  3. Salvatore Longo
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  10. Dario Lazzarino
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  11. Giuseppe Lazzarino
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  12. Barbara Tavazzi
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Correspondence to Giuseppe Lazzarino.

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Amorini, A.M., Giorlandino, C., Longo, S. et al. Metabolic profile of amniotic fluid as a biochemical tool to screen for inborn errors of metabolism and fetal anomalies. Mol Cell Biochem 359, 205–216 (2012). https://doi.org/10.1007/s11010-011-1015-y

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  • DOI: https://doi.org/10.1007/s11010-011-1015-y

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