A Folate-Dependent Metabolite in Amniotic Fluid from Pregnancies with Normal or Trisomy 21 Chromosomes

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

doi:10.1159/000089066

Cited by 7 publications

(5 citation statements)

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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

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“…Interestingly, individuals with Down syndrome have elevated purine levels in bodily fluids and this has been hypothesised to be due to trisomy of GART and resultant increased synthesis of purines [35,36] . A number of investigators have speculated on the trisomy of the gene for cystathionine beta synthase (CBS), located on chromosome 21, in the possible role of enzyme polymorphisms and dietary response to folates [15,20,31,37,38] . CBS synthesises cystathionine from homocysteine and serine.…”

Section: Updatesmentioning

confidence: 99%

“…Thus, it might increase the availability of 1-C units. Indeed, reduced levels of FIGLU have been found in the amniotic fluid of pregnancies with Down syndrome [37] . Thus, an added complexity to the genotype of the mother is the possible effect of trisomy of these genes in the foetus with Down syndrome.…”

Section: Updatesmentioning

confidence: 99%

Folate metabolism and the risk of Down syndrome

Patterson¹

2008

Downs Syndr. Res. Pract.

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“…Decreased transfer results in decrease methylation of DNA around the centromere region of chromosome 21, 18 and 13 proposed to be leading to aneuploidy. This hypothesis has led many researchers to further explore the evidence between DNA methylation of chromosome 21, 18, 13 in the unfertilized ovum but due to invasive nature of method involved in acquiring the pre-implementation studies, it has not been proven [10,[12][13][14][15][16].…”

Section: Introductionmentioning

confidence: 99%

Methyl Tetra Hydro Folate Reductase Enzyme Polymorphism in the Mothers with Previous Autosomal Aneuploidy Birth in the Indigenous African Population of Northern Region of South Africa

Duma¹,

Khine²

2017

J Down Syndr Chr Abnorm

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IntroductionAneuploidy is a genetic disorder where the total number of chromosomes is either less or more than the normal diploid number of 46, XX or 46, XY [1]. The most common aneuploidies in South Africa caused by autosomal chromosomal abnormalities include Down syndrome (Trisomy 21), Edward syndrome (Trisomy 18) and Patau syndrome (Trisomy 13). Globally the incidence for Down syndrome is about 1 in 650 to 1000 live births [2], Edward syndrome is 1 in 6000 live birth [3], and Patau is between 1 in 5000 to 29000 live birth [4]. Currently the prevalence rate is 1 out of 500 live birth for Down syndrome in South Africa with 1886 new cases diagnosed every year [5] and for Edward syndrome the prevalence is 1 in 4000 live birth and Patau is 1 in 8889 live birth [6,7]. The aetiology of these autosomal aneuploidies are believed to be due to non-disjunction of chromosome in maternal ovum during meiosis which is thought to be a sporadic, incidental event usually associated with older age group mothers. Notably, there is an increased incidence of aneuploidy babies has been observed in younger age group mothers with less than 35 years of age in South African black population [8].There were studies done in the Middle East families with recurrence aneuploidy births to determine if there is a genetic link. Krishna Murthy and Farag reported two unrelated Kuwaiti families each having 3 siblings with trisomy 21 as a result the researchers suggested that some genetic predisposition and gonadal mosaicism could be the underlying cause of recurrent aneuploidy in the younger mothers, thus increasing the risk of recurrence of such pregnancies [9]. There were studies that found that a particular polymorphism of one of these genes Methylenetetrahydrofolate reductase (MTHFR) might be a maternal risk factor for having child with Aneuploidy or Down syndrome and that a significant increase in plasma homocysteine levels exists in mothers of the children with Aneuploidy or Down syndrome [10,11].Increased homocysteine may result from dietary deficiency of folate and or vitamin B12 or from genetic polymorphism of Methylenetetrahydrofolate reductase (MTHFR). These genes encode the enzymes involved in the transfer of methyl group from sulpha containing amino acids (homocysteine and cysteine). Decreased transfer results in decrease methylation of DNA around the centromere region of chromosome 21, 18 and 13 proposed to be leading to aneuploidy. This hypothesis has led many researchers to further explore the evidence between DNA methylation of chromosome 21, 18, 13 in the unfertilized ovum but due to invasive nature of method involved in acquiring the pre-implementation studies, it has not been proven [10,[12][13][14][15][16].Indirect evidence of younger mothers having high level of plasma homocysteine with or without genetic polymorphisms would be the closest link to identifying the risk of recurrence aneuploidy in the AbstractBackground and purpose of the study: Aneuploidy births are highly prevalent in our population and some families, recurre...

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A Folate-Dependent Metabolite in Amniotic Fluid from Pregnancies with Normal or Trisomy 21 Chromosomes

Cited by 7 publications

References 24 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

Folate metabolism and the risk of Down syndrome

Methyl Tetra Hydro Folate Reductase Enzyme Polymorphism in the Mothers with Previous Autosomal Aneuploidy Birth in the Indigenous African Population of Northern Region of South Africa

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