Pyridoxine-Related Metabolite Concentrations in Normal and Down Syndrome Amniotic Fluid

Baggot, Paddy Jim; Eliseo, Anna Jane Y.; DeNicola, Nathaniel; Kalamarides, Jeremy A.; Shoemaker, James D.

doi:10.1159/000123610

Cited by 5 publications

(1 citation statement)

References 17 publications

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“…The toxic effects of pharmaceuticals and their mitigation by vitamin supplementation has been reported (12). Amniotic fluid samples from normal and Down syndrome pregnancies were analyzed and reported (13)(14)(15).…”

Section: Discussionmentioning

confidence: 99%

One-step Metabolomics: Carbohydrates, Organic and Amino Acids Quantified in a Single Procedure

Shoemaker

2010

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Every infant born in the US is now screened for up to 42 rare genetic disorders called "inborn errors of metabolism". The screening method is based on tandem mass spectrometry and quantifies acylcarnitines as a screen for organic acidemias and also measures amino acids. All states also perform enzymatic testing for carbohydrate disorders such as galactosemia. Because the results can be non-specific, follow-up testing of positive results is required using a more definitive method. The present report describes the "urease" method of sample preparation for inborn error screening. Crystalline urease enzyme is used to remove urea from body fluids which permits most other water-soluble metabolites to be dehydrated and derivatized for gas chromatography in a single procedure. Dehydration by evaporation in a nitrogen stream is facilitated by adding acetonitrile and methylene chloride. Then, trimethylsilylation takes place in the presence of a unique catalyst, triethylammonium trifluoroacetate. Automated injection and chromatography is followed by macro-driven custom quantification of 192 metabolites and semi-quantification of every major component using specialized libraries of mass spectra of TMS derivatized biological compounds. The analysis may be performed on the widely-used Chemstation platform using the macros and libraries available from the author. In our laboratory, over 16,000 patient samples have been analyzed using the method with a diagnostic yield of about 17%--that is, 17% of the samples results reveal findings that should be acted upon by the ordering physician. Included in these are over 180 confirmed inborn errors, of which about 38% could not have been diagnosed using previous methods. Video LinkThe video component of this article can be found at

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Section: Discussionmentioning

confidence: 99%

One-step Metabolomics: Carbohydrates, Organic and Amino Acids Quantified in a Single Procedure

Shoemaker

2010

JoVE

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Amniotic Fluid

BCh

Frcp²,

Facmg³

et al. 2009

Genetic Disorders and the Fetus

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Screening and Predictive Biomarkers for Down Syndrome Through Amniotic Fluid Metabolomics

Zhang,

Yang,

Jiang

et al. 2024

Prenatal Diagnosis

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BackgroundDown syndrome (DS) is a congenital disorder caused by the presence of an extra copy of all or part of chromosome 21. It is characterized by significant intellectual disability, distinct facial features, and growth and developmental challenges. The utilization of metabolomics to analyze specific metabolic markers in maternal amniotic fluid may provide innovative tools and screening methods for investigating the early pathophysiology of trisomy 21 at the functional level.MethodsAmniotic fluid samples were obtained via amniocentesis from 57 pregnancies with DS and 55 control pregnancies between 173/7 and 240/7 weeks of gestation. The targeted metabolomics focused on 34 organic acids, 17 amino acids, and 5 acylcarnitine metabolites. The untargeted metabolomics analysis concentrated on lipid profiles and included 602 metabolites that met quality control standards. Principal Component Analysis, Orthogonal Partial Least Squares Discriminant Analysis (OPLS‐DA), and false discovery rate (FDR) adjustments were applied. MetaboAnalystR 5.0 was used to perform the metabolic pathway analysis on the identified differential metabolites.ResultsFifty differential metabolites, including L‐glutamine, eight organic acids, and 41 lipids, were significantly altered in DS based on three criteria: VIP > 1 in the OPLS‐DA model, FDR‐adjusted p‐value < 0.05, and |log2FC| > log2(1.5) from a volcano plot of all detected metabolites. An analysis of 212 differential metabolites, selected from both targeted and untargeted approaches (VIP > 1 in the OPLS‐DA model and FDR‐adjusted p‐value < 0.05), revealed significant changes in nine metabolic pathways. Fourteen key metabolites were identified to establish a screening model for DS, achieving an area under the curve of 1.00.ConclusionsOur results underscore the potential of metabolomics approaches in identifying concise and reliable biomarker combinations that demonstrate promising screening performance in DS.

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Pyridoxine-Related Metabolite Concentrations in Normal and Down Syndrome Amniotic Fluid

Cited by 5 publications

References 17 publications

One-step Metabolomics: Carbohydrates, Organic and Amino Acids Quantified in a Single Procedure

One-step Metabolomics: Carbohydrates, Organic and Amino Acids Quantified in a Single Procedure

Amniotic Fluid

Screening and Predictive Biomarkers for Down Syndrome Through Amniotic Fluid Metabolomics

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