Abnormalities in the genes that encode Large Amino Acid Transporters increase the risk of Autism Spectrum Disorder

Objectives Autism spectrum disorders and intellectual disability present a challenge for therapeutic and dietary management. We performed a re-analysis of plasma amino acid chromatography of children with autism spectrum disorders ( n = 22) or intellectual disability ( n = 29) to search for a metabolic signature that can distinguish individuals with these disorders from controls ( n = 30). Methods We performed univariate and multivariate analyses using different machine learning strategies, from the raw data of the amino acid chromatography. Finally, we analysed the metabolic pathways associated with discriminant biomarkers. Results Multivariate analysis revealed models to discriminate patients with autism spectrum disorders or intellectual disability and controls from plasma amino acid profiles ( P < 0.0003). Univariate analysis showed that autism spectrum disorder and intellectual disability patients shared similar differences relative to controls, including lower glutamate ( P < 0.0001 and P = 0.0002, respectively) and serine ( P = 0.002 for both) concentrations. The multivariate model ( P < 6.12.10−7) to discriminate between autism spectrum disorders and intellectual disability revealed the involvement of urea, 3-methyl-histidine and histidine metabolism. Biosigner analysis and univariate analysis confirmed the role of 3-methylhistidine ( P = 0.004), histidine ( P = 0.003), urea ( P = 0.0006) and lysine ( P = 0.002). Conclusions We revealed discriminant metabolic patterns between autism spectrum disorders, intellectual disability and controls. Amino acids known to play a role in neurotransmission were discriminant in the models comparing autism spectrum disorders or intellectual disability to controls, and histidine and b-alanine metabolism was specifically highlighted in the model.

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The risk of malnutrition in children with autism spectrum disorder

Archives of Disease in Childhood - Education and Practice ◽

10.1136/archdischild-2019-317453 ◽

2019 ◽

pp. edpract-2019-317453

Author(s):

Lydia Iris Healy ◽

Eimear Forbes ◽

Jane Rice ◽

Jane M Leonard ◽

Ellen Crushell

Keyword(s):

Autism Spectrum Disorder ◽

Vitamin E ◽

Amino Acid ◽

Autism Spectrum ◽

Spectrum Disorder ◽

French Fries ◽

Calorie Intake ◽

Acid Oxidation ◽

List Type ◽

Dietary Analysis

A 9-year-old boy presented with a 2-day history of vomiting, ataxia and reduced consciousness. He had vomited intermittently in the two preceding months, without headaches, visual disturbance or early morning symptoms. He had autism spectrum disorder, and restricted eating since aged 2 years, eating only corn-crisps, Rich Tea biscuits and chips (French fries), and drinking Coca-Cola (containing 10% glucose; figure 1). Recently a dietician had prescribed a multivitamin.Figure 1The patient's complete daily food intake over approximately 7 years (2-3 biscuits per day).Dietary analysis revealed an extremely low protein (0.37 g/kg/day) and low fat (0.77 g/kg/day) diet for over 7 years with a caloric intake of 1200 kCal. Estimated requirements were 1512 kCal,1 0.92 mg/kg/day of protein2 and 1.94 mg/kg of fat (based on 35% of daily calorie intake3).On examination he was encephalopathic, with hepatomegaly and ascites. His height and weight were on the 0.4th–2nd and 9th centiles, respectively. Laboratory results demonstrated glucose 2.7 mmol/L, mild anaemia, raised urea (10.7 mmol/L) with normal creatinine and raised hepatic transaminases, low albumin and elevated creatinine kinase (peak 7809 IU/L). He remained encephalopathic and was intubated for poor respiratory function. Ammonia and blood pH were normal.Question 1What nutritional/metabolic test(s) would be the next best step?Vitamin B1 (thiamine) levelsCopper and caeruloplasmin levelsBlood spot for acylcarnitine profilePlasma amino acid profileUrine organic acidsQuestion 2What potentially dangerous feeding issues in paediatric intensive care exist here?Electrolyte levels and supplementationFat composition of feedsAmino acid composition of feedsVitamin levelsQuestion 3Why might this patient have had preserved vitamin E levels?Vitamin E is added to rancherosSome vitamin E is obtained from sunlightFrench fries are relatively high in vitamin EMultivitamin preparationsQuestion 4What metabolic disorders are associated with very low carnitine levels?Organic acidaemiasFatty acid oxidation disordersMitochondrial disorders (disorders of respiratory chain)Maple syrup urine disease (MSUD)Answers can be found on page 01

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Impaired Amino Acid Transport at the Blood Brain Barrier Is a Cause of Autism Spectrum Disorder

Cell ◽

10.1016/j.cell.2016.11.013 ◽

2016 ◽

Vol 167 (6) ◽

pp. 1481-1494.e18 ◽

Cited By ~ 119

Author(s):

Dora C. Tărlungeanu ◽

Elena Deliu ◽

Christoph P. Dotter ◽

Majdi Kara ◽

Philipp Christoph Janiesch ◽

...

Keyword(s):

Autism Spectrum Disorder ◽

Amino Acid ◽

Blood Brain Barrier ◽

Amino Acid Transport ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Brain Barrier ◽

Acid Transport ◽

Blood Brain

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Reduction of essential amino acid levels and sex-specific alterations in serum amino acid concentration profiles in children with autism spectrum disorder

Psychiatry Research ◽

10.1016/j.psychres.2020.113675 ◽

2020 ◽

pp. 113675

Author(s):

Xing Yu ◽

Lv Qian-Qian ◽

You Cong ◽

Zou Xiao-Bing ◽

Deng Hong-Zhu

Keyword(s):

Autism Spectrum Disorder ◽

Amino Acid ◽

Acid Concentration ◽

Essential Amino Acid ◽

Children With Autism ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Amino Acid Concentration ◽

Concentration Profiles ◽

Amino Acid Levels

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Altered Glutamate and Glutamine Kinetics in Autism Spectrum Disorder

Current Developments in Nutrition ◽

10.1093/cdn/nzab047_008 ◽

2021 ◽

Vol 5 (Supplement_2) ◽

pp. 845-845

Author(s):

Sofie De Wandel ◽

Marielle PKJ Engelen ◽

Raven Wierzchowska-McNew ◽

Julie Thompson ◽

Sarah K Kirschner ◽

...

Keyword(s):

Autism Spectrum Disorder ◽

Amino Acid ◽

Pearson Correlation ◽

Plasma Concentrations ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Word Fluency ◽

Attention Switching ◽

Neurocognitive Dysfunction ◽

Mood Changes

Abstract Objectives Recent studies suggest that glutamate (GLU) signaling abnormalities are involved in the etiology of Autism Spectrum Disorder (ASD), suggesting perturbations in GLU and glutamine (GLN) metabolism. Although GLU and GLN plasma concentrations have been linked to cognitive decline, the actual production of GLU and GLN have never been measured in ASD and linked to ASD severity score and neurocognitive and mood changes. Methods 19 young adults with high functioning ASD (age 24.3 ± 1.0y, Autism Quotient (AQ): 31.4 ± 1.7), and 46 control subjects (age 23.4 ± 0.3y)) were enrolled. ASD severity and subscores as well as cognitive function and mood were assessed (MOCA, TMT, word fluency, Stroop, HADS). Postabsorptive amino acid kinetics (production of GLU and GLN, and its interconversion rates (GLU > >GLN and GLN > >GLU)) were measured by pulse stable isotope administration and subsequent blood sampling for 4 hours. Plasma amino acid enrichments and concentrations were analyzed by LC-MS/MS. Stats were done by ANCOVA, post hoc analysis and Pearson correlation. Significance was set at p < 0.05. Results No differences were present in word fluency, but higher values in ASD for TMTb (p = 0.066), depression (p = 0.0004), anxiety (p = 0.0006) and lower values for MOCA (0.0054). The ASD group was characterized by lower plasma GLN and GLU concentrations (p < 0.05). Although the production rates of GLN and GLU were not different between the groups, in ASD GLN > >GLU was higher (p = 0.0018) and GLU > >GLN lower (p = 0.016) and a higher GLN clearance rate (p = 0.006). Significant relationships were found in the ASD group between several GLU and GLN kinetic markers and AQ subscores (e.g., attention to detail, attention switching and/or communication) and word fluency (p < 0.05). Conclusions Disturbances in GLN and GLU metabolism in ASD are associated with changes in ASD subscores but less with neurocognitive dysfunction or mood changes. Funding Sources None.

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