Autism

Thomas M Maynard et al. Balancing Act: Maintaining Amino Acid Levels in the Autistic Brain. Neuron. 2017 Feb 8;93(3):476-479.

Alan M Smith et al. A Metabolomics Approach to Screening for Autism Risk in the Children’s Autism Metabolome Project. Autism Res. 2020 Aug;13(8):1270-1285

Analysis of a selected set of metabolites in blood samples from children with autism and typically developing children identified reproducible differences in the metabolism of about half of the children with autism. Testing for these differences in blood samples can be used to help screen children as young as 18 months for risk of autism that, in turn, can facilitate earlier diagnoses.

Alan M Smith et al. Amino acid dysregulation metabotypes: potential biomarkers for diagnosis and individualized treatment for subtypes of autism spectrum disorder. Biol Psychiatry. 2019 Feb 15; 85(4): 345–354.

Identification and utilization of metabotypes of ASD can lead to actionable metabolic tests that support early diagnosis and stratification for targeted therapeutic intervention.

Anatoly V. Skalny et al. Serum amino acid spectrum in children with autism spectrum disorder (ASD. Research in Autism Spectrum Disorders September 2020 77:101605

Maria Vittoria Ristori et al. Proteomics and Metabolomics Approaches towards a Functional Insight onto AUTISM Spectrum Disorders: Phenotype Stratification and Biomarker Discovery. Int J Mol Sci. 2020 Aug 30;21(17):6274.

Martina Montanari et al. Autism spectrum disorder: Focus on Glutamatergic Neurotransmission. Int J Mol Sci. 2022 Mar 31;23(7):3861.

Fatir Qureshi et al. Multivariate Analysis of Metabolomic and Nutritional Profiles among Children with Autism Spectrum Disorder. J Pers Med. 2022 Jun 1;12(6):923.
Areej Mesleh et al. Blood Proteomics Analysis Reveals Potential Biomarkers and Convergent Dysregulated Pathways in Autism Spectrum Disorder: A Pilot Study. Int J Mol Sci. 2023 Apr 18;24(8):7443.

Laura Hewitson et al. Blood biomarker discovery for autism spectrum disorder: A proteomic analysis. PLoS One. 2021 Feb 24;16(2):e0246581.

Brittany D Needham et al. Plasma and Fecal Metabolite Profiles in Autism Spectrum Disorder. Biol Psychiatry. 2021 Mar 1;89(5):451-462.

Troy Vargason et al. Towards a Multivariate Biomarker-Based Diagnosis of Autism Spectrum Disorder: Review and Discussion of Recent Advancements. Semin Pediatr Neurol. 2020 Jul;34:100803.

Troy Vargason et al. Investigating Plasma Amino Acids for Differentiating Individuals with Autism Spectrum Disorder and Typically Developing Peers. Res Autism Spectr Disord. 2018 Jun;50:60-72.

Mingyang Zou et al. Identification of Amino Acid Dysregulation as a Potential Biomarker for Autism Spectrum Disorder in China. Neurotox Res. 2020 Dec;38(4):992-1000.

Martina Randazzo et al. Neuroactive Amino Acid Profile in Autism Spectrum Disorder: Results from a Clinical Sample. Children (Basel). 2023 Feb 20;10(2):412.

Attia Anwar et al. Advanced glycation endproducts, dityrosine and arginine transporter dysfunction in autism – a source of biomarkers for clinical diagnosis. Mol Autism. 2018 Feb 19;9:3.

Rita Barone et al. A Subset of Patients with Autism Spectrum Disorders Show a Distinctive Metabolic Profile by Dried Blood Spot Analyses. Front Psychiatry. 2018 Dec 7;9:636.

Hui-Fei Zheng et al. Body fluid levels of neuroactive amino acids in autism spectrum disorders: a review of the literature. Amino Acids. 2017 Jan;49(1):57-65.

Dora C Tărlungeanu et al. Impaired Amino Acid Transport at the Blood Brain Barrier Is a Cause of Autism Spectrum Disorder. Cell. 2016 Dec 1;167(6):1481-1494.e18.

Our data elucidate a neurological syndrome defined by SLC7A5 mutations and support an essential role for the BCAA in human brain function.

García-Cazorla A. Two novel mutations in the BCKDK (branched-chain keto-acid dehydrogenase kinase) gene are responsible for a neurobehavioral deficit in two pediatric unrelated patients. Hum Mutat. 2014 Apr;35(4):470-7.

Based on these results, a protein-rich diet plus oral BCAA supplementation was implemented in the patient homozygous for p.R174Gfs1. This treatment normalized plasma BCAA levels and improved growth, developmental and behavioral variables. Our results demonstrate that BCKDK mutations can result in neurobehavioral deficits in humans and support the rationale for dietary intervention.

Arnold GL . Plasma amino acids profiles in children with autism: potential risk of nutritional deficiencies. J Autism Dev Disord. 2003 Aug;33(4):449-54.

Children with autism had more essential amino acid deficiencies consistent with poor protein nutrition than an age/gender matched control group. There was a trend for children with autism who were on restricted diets to have an increased prevalence of essential amino acid deficiencies and lower plasma levels of essential acids including the neurotransmitter precursors tyrosine and tryptophan than both controls and children with autism on unrestricted diets.

Tu WJ. Application of LC-MS/MS analysis of plasma amino acids profiles in children with autism. J Clin Biochem Nutr. 2012 Nov;51(3):248-9.

Shimmura C. Alteration of plasma glutamate and glutamine levels in children with high-functioning autism. PLoS One. 2011;6(10):e25340.

Zhen Zheng et al. Blood Glutamate Levels in Autism Spectrum Disorder: A Systematic Review and Meta-Analysis. PLoS One. 2016 Jul 8;11(7):e0158688.

Ghanizadeh A. Increased glutamate and homocysteine and decreased glutamine levels in autism: a review and strategies for future studies of amino acids in autism. Dis Markers. 2013;35(5):281-6

Novarino G. Mutations in BCKD-kinase lead to a potentially treatable form of autism with epilepsy. Science. 2012 Oct 19;338(6105):394-7.

Bckdk knockout mice show abnormal brain amino acid profiles and neurobehavioral deficits that respond to dietary supplementation. Thus, autism presenting with intellectual disability and epilepsy caused by BCKDK mutations represents a potentially treatable syndrome.

Stokstad E. Development. New hints into the biological basis of autism. Science. 2001 Oct 5; 294 (5540): 34-7

Paul R West et al. Metabolomics as a tool for discovery of biomarkers of autism spectrum disorder in the blood plasma of children. PLoS One. 2014 Nov 7;9(11):e112445.

Joris H J van Sadelhoff et al. The Gut-Immune-Brain Axis in Autism Spectrum Disorders; A Focus on Amino Acids. Front Endocrinol (Lausanne). 2019 Apr 16;10:247.

Senthilkumar Rajagopal et al. Modulatory Effects of Dietary Amino Acids on Neurodegenerative Diseases. Adv Neurobiol. 2016;12:401-14.