Amino acid profile in Down's syndrome.

Heggarty, Hugh; Ball, Ronald O.; Smith, Mark; Henderson, M J

doi:10.1136/adc.74.4.347

Cited by 10 publications

(6 citation statements)

References 1 publication

Supporting

Mentioning

Contrasting

Order By: Relevance

“…(4) Beside the distinct neurocognitive phenotype, differences in the metabolic pro les have been observed in individuals with DS. (5)(6)(7) Additionally, the involvement of reactive oxygen species (ROS) has been observed in some of the DS pathologies. The gene coding for Cu/Zn-superoxide dismutase (also known as SODL) is found on chromosome21 in humans.…”

Section: Introductionmentioning

confidence: 99%

WITHDRAWN: Use of antioxidants supplementation on developmental outcomes in children with Down Syndrome - a systematic review and meta-analyses

Jafri¹,

Iqbal

Alam

et al. 2021

Preprint

View full text Add to dashboard Cite

AIM To evaluate the published literature on the use of antioxidants in improving developmental outcomes in DS children METHODS The systematic review included interventional studies (randomized controlled trials (RCTs) and quasi-RCTs (q-RCTs)) on children between the ages of 0 to 18 years diagnosed with DS and used antioxidants for improving developmental outcomes, and compered with similar children given placebo or no supplementation. Aim was to have a true randomized population for intervention, thus RCTs and quasi- RCTs were included. Studies were excluded if those were non-randomized controlled studies (including observational studies, systematic and narrative review articles, editorials and commentaries) with no random allocation and no comparison group. We also excluded studies if data from participants with DS was included as part of a larger group of participants (e.g. children with intellectual disability) and could not be separated for subgroup analysis, and studies that did not assess developmental domains and only assessed biochemical markers. The review included children with other conditions associated with developmental disability, only when data for children with DS were separately reported. RESULTS Eleven RCTs and q-RCTs fulfilled the eligibility criteria with 683 participants with Down syndrome, with age range of newborns to 17 years of age. Eight studies did not show any statistically significant clinical benefit of using antioxidants. A meta-analysis was applied to compare changes in the effect sizes (post and pre-intervention) in GDQ between the intervention and control groups. The forest plot including the three studies doesn’t demonstrate a statistically significant improvement. INTERPRETATION This review concludes that the use of antioxidants does not improve the developmental outcomes in pediatric population with DS.

show abstract

Section: Introductionmentioning

confidence: 99%

WITHDRAWN: Use of antioxidants supplementation on developmental outcomes in children with Down Syndrome - a systematic review and meta-analyses

Jafri¹,

Iqbal

Alam

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…Alteration of chromosome content can therefore be hypothesized to alter the subcellular machinery and these changes would be manifest by an alteration in blastomere metabolism. In support of this idea, individuals with trisomy 21 have altered plasma amino acid levels (Lejeune et al, 1992;Heggarty et al, 1996), including lysine and serine. Furthermore, in trisomic mice, the activity of certain enzymes involved in amino acid metabolism is affected (Vaisman et al, 1981).…”

Section: Discussionmentioning

confidence: 98%

Association between amino acid turnover and chromosome aneuploidy during human preimplantation embryo development in vitro

Picton

Elder

Houghton

et al. 2010

Molecular Human Reproduction

102

View full text Add to dashboard Cite

This study investigated the relationship between human preimplantation embryo metabolism and aneuploidy rates during development in vitro. One hundred and eighty-eight fresh and cryopreserved embryos from 59 patients (33.9 +/- 0.6 years) were cultured for 2-5 days. The turnover of 18 amino acids was measured in spent media by high-performance liquid chromatography. Embryos were either fixed for interphase fluorescent in situ hybridization analysis of chromosomes 13, 18, 19, 21, X or Y, or were assayed for mitochondrial activity. Amino acid turnover was different (P < 0.05) between stage-matched fresh and cryopreserved embryos due to blastomere loss following warming. The proportion of embryos with aneuploid cells increased as cell division progressed from pronucleate- (23%) to late cleavage stages (50-70%). Asparagine, glycine and valine turnover was significantly different between uniformly genetically normal and uniformly abnormal embryos on Days 2-3 of culture. By Days 3-4, the profiles of serine, leucine and lysine differed between uniformly euploid versus aneuploid embryos. Gender significantly (P < 0.05) affected the metabolism of tryptophan, leucine and asparagine by cleavage-stage embryos. Pronucleate zygotes had a significantly higher proportion of active:inactive mitochondria compared with cleavage-stage embryos. Furthermore, mitochondrial activity was correlated (P < 0.05) with altered aspartate and glutamine turnover. These results demonstrate the association between the metabolism, cytogenetic composition and health of human embryos in vitro.

show abstract

“…If the standard error of the mean (SEM) is reported, standard deviations can be derived by using the formula: SD = SEM*sqrt(N). This conversion was performed on the following studies: Stocchi et al 1985 , Valenti et al 2010 , Rodríguez-Sureda et al 2015 , Izzo et al 2017 , Heggarty et al 1996 , Watkins et al 1989 , Tiano et al 2008 , and Convertini et al 2016 .…”

Section: Gene Expression Proteomic and Metabolomic Profiling Of Ds Amentioning

confidence: 99%

Meta-analysis of metabolites involved in bioenergetic pathways reveals a pseudohypoxic state in Down syndrome

Pecze

Randi

Szabó

2020

Mol Med

View full text Add to dashboard Cite

Clinical observations and preclinical studies both suggest that Down syndrome (DS) may be associated with significant metabolic and bioenergetic alterations. However, the relevant scientific literature has not yet been systematically reviewed. The aim of the current study was to conduct a meta-analysis of metabolites involved in bioenergetics pathways in DS to conclusively determine the difference between DS and control subjects. We discuss these findings and their potential relevance in the context of pathogenesis and experimental therapy of DS. Articles published before July 1, 2020, were identified by using the search terms “Down syndrome” and “metabolite name” or “trisomy 21” and “metabolite name”. Moreover, DS-related metabolomics studies and bioenergetics literature were also reviewed. 41 published reports and associated databases were identified, from which the descriptive information and the relevant metabolomic parameters were extracted and analyzed. Mixed effect model revealed the following changes in DS: significantly decreased ATP, CoQ10, homocysteine, serine, arginine and tyrosine; slightly decreased ADP; significantly increased uric acid, succinate, lactate and cysteine; slightly increased phosphate, pyruvate and citrate. However, the concentrations of AMP, 2,3-diphosphoglycerate, glucose, and glutamine were comparable in the DS vs. control populations. We conclude that cells of subjects with DS are in a pseudo-hypoxic state: the cellular metabolic and bio-energetic mechanisms exhibit pathophysiological alterations that resemble the cellular responses associated with hypoxia, even though the supply of the cells with oxygen is not disrupted. This fundamental alteration may be, at least in part, responsible for a variety of functional deficits associated with DS, including reduced exercise difference, impaired neurocognitive status and neurodegeneration.

show abstract

Amino acid profile in Down's syndrome.

Cited by 10 publications

References 1 publication

WITHDRAWN: Use of antioxidants supplementation on developmental outcomes in children with Down Syndrome - a systematic review and meta-analyses

WITHDRAWN: Use of antioxidants supplementation on developmental outcomes in children with Down Syndrome - a systematic review and meta-analyses

Association between amino acid turnover and chromosome aneuploidy during human preimplantation embryo development in vitro

Meta-analysis of metabolites involved in bioenergetic pathways reveals a pseudohypoxic state in Down syndrome

Contact Info

Product

Resources

About