Email Alert | RSS

Journal of Peking University (Health Sciences) ›› 2025, Vol. 57 ›› Issue (2): 277-283. doi: 10.19723/j.issn.1671-167X.2025.02.009

Previous Articles     Next Articles

Change of plasma level of valine and its relationship with developmental quotient in children with autism

Xinjie XU1, Xiaoe CAI2, Fanchao MENG3, Bo LONG1, Xin YOU4, Rong ZHANG5,*()   

  1. 1. Medical Science Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China
    2. Department of Rehabilitation Medicine, Beijing Haidian Hospital, Beijing 100080, China
    3. The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing 100088, China
    4. Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China
    5. Neuroscience Research Institute, Peking University; Department of Neurobiology, Peking University School of Basic Medical Sciences; Key Laboratory for Neuroscience, Ministry of Education/National Health and Family Planning Commission; Autism Research Center of Peking University Health Science Center, Beijing 100191, China
  • Received:2021-11-16 Online:2025-04-18 Published:2025-04-12
  • Contact: Rong ZHANG E-mail:zhangrong@bjmu.edu.cn
  • Supported by:
    the Beijing-Tianjin-Hebei Basic Research Cooperation Special Project(J230013);the National Natural Science Foundation of China(81601196)

RICH HTML

   

PDF (PC)

Abstract:

Objective: To compare the differences of plasma valine level between autistic and healthy children, and to explore the relationship between plasma valine level and developmental quotient in children with autism. Methods: In this study, a total of 29 autistic children and 30 typically developing children of the same age range were recruited as the autistic group and the control group. The childhood autism rating scale (CARS) was used to assess autistic core symptoms and severity in the autistic children. Children's developmental quotient was evaluated by Gesell developmental schedules (GDS), and plasma valine level was measured by high performance liquid chromatography-tandem mass spectrometry. The correlation between plasma valine level and developmental quotient scores in the autistic group was analyzed. Results: The plasma level of valine in the autism group was significantly lower than in the control group (P < 0.05). Children in the autism group got significantly lower scores in the adaption, gross motor, fine motor, language function and personal/social function subscales in GDS than in the control group (P < 0.000 1). Plasma valine level in the autism group showed significant positive correlations with scores of the fine motor (r=0.441, P < 0.05) and personal/social function (r=0.437, P < 0.05) subscales in GDS, but showed no significant correlations with scores of the adaption, gross motor and language function subscales in GDS (P>0.05). According to the criteria of CARS, children in the autism group were subdivided into the mild to moderate subgroup and the severe subgroup based on the severity of the autistic symptoms. Compared with children in the mild to moderate subgroup, children in the severe subgroup got significantly lower scores in the adaption, fine motor, language function and personal/social function subscales in GDS (P < 0.05), while there was no significant difference between the two subgroups in gross motor scores and plasma valine level (P>0.05). Conclusion: The level of valine in plasma of autistic children is relatively lower, and there is a certain relationship between plasma valine level and the fine movement and personal/social function among children with autism.

Key words: Autism, Valine, Developmental quotient

CLC Number: 

  • R749.94

Table 1

Comparison of general data between children in the two groups"

Items Autism group Control group Statistic value P
n 29 30
Age/years, ${\bar x}$±s 4.55±1.03 4.42±0.77 t = 0.582 0.563
Gender (male) 29 30 >0.999
CARS, ${\bar x}$±s 35.34±4.12 NA

Figure 1

Comparison of plasma valine levels between children in the autism and control groups"

Table 2

Comparison of GDS scores between children in the two groups"

Items Autism group, ${\bar x}$±s Control group, ${\bar x}$±s t P
Adaption 59.41±17.79 99.57±10.62 8.934 ＜0.000 1
Gross motor 71.45±13.30 108.43±19.97 9.919 ＜0.000 1
Fine motor 67.77±17.96 96.38±7.10 6.808 ＜0.000 1
Language function 49.55±16.79 99.57±11.04 11.490 ＜0.000 1
Personal/social function 62.41±15.16 103.38±15.48 8.766 ＜0.000 1

Figure 2

Relationship between plasma valine levels and GDS fine motor scores (A) and personal/social function scores (B) in autistic children GDS, Gesell developmental schedules."

Table 3

Relationship between plasma valine levels and GDS scores in autism and control groups"

Group GDS scores
Adaption Gross motor Fine motor Language function Personal/social function
Autism group r 0.365 0.238 0.441 0.242 0.437
P 0.095 0.286 0.040 0.276 0.042
Control group r 0.168 0.057 -0.185 0.224 0.093
P 0.467 0.807 0.422 0.328 0.688

Table 4

Comparison of plasma valine levels and GDS scores between mild to moderate autism and severe autism subgroups"

Autism subgroups Valine, ${\bar x}$±s GDS scores, ${\bar x}$±s
Adaption Gross motor Fine motor Language function Personal/social function
Mild to moderate 6.11±0.81 67.75±14.72 74.42±13.08 77.75±13.65 56.33±15.89 68.75±14.23
Severe 5.76±1.03 49.40±16.43 67.90±13.35 55.80±15.25 41.40±14.62 54.8±13.08
P 0.317 0.012 0.262 0.002 0.034 0.028
1 González MC , Vásquez M , Hernández-Chávez M . Autism spectrum disorder: Clinical diagnosis and ADOS test[J]. Rev Chil Pediatr, 2019, 90 (5): 485- 491.
2 Maenner MJ , Shaw KA , Baio J , et al. Prevalence of autism spectrum disorder among children aged 8 years: Autism and Developmental Disabilities Monitoring Network, 11 Sites, United States, 2016[J]. MMWR Surveill Summ, 2020, 69 (4): 1- 12.
doi: 10.15585/mmwr.ss6904a1
3 Zhou H , Xu X , Yan W , et al. Prevalence of autism spectrum disorder in China: A nationwide multi-center population-based study among children aged 6 to 12 years[J]. Neurosci Bull, 2020, 36 (9): 961- 971.
doi: 10.1007/s12264-020-00530-6
4 樊越波, 揭晓锋, 邹小兵. 孤独症患病率回顾[J]. 中国儿童保健杂志, 2008, 16 (4): 439- 440.
doi: 10.3969/j.issn.1008-6579.2008.04.029
5 Croen LA , Zerbo O , Qian Y , et al. The health status of adults on the autism spectrum[J]. Autism, 2015, 19 (7): 814- 823.
doi: 10.1177/1362361315577517
6 赵刚, 韦明, 鄂颖梅, 等. 孤独症谱系障碍儿童饮食行为与家长喂养行为的相关研究[J]. 沈阳医学院学报, 2020, 22 (5): 428- 432.
7 Ghanizadeh A . Increased glutamate and homocysteine and decreased glutamine levels in autism: A review and strategies for future studies of amino acids in autism[J]. Dis Markers, 2013, 35 (5): 281- 286.
8 National Center for Biotechnology Information (2024). PubChem compound summary for CID 6287, valine[EB/OL]. [2021-03-08] https://pubchem.ncbi.nlm.nih.gov/compound/Valine.
9 Maynard TM , Manzini MC . Balancing act: Maintaining amino acid levels in the autistic brain[J]. Neuron, 2017, 93 (3): 476- 479.
doi: 10.1016/j.neuron.2017.01.015
10 Tǎrlungeanu DC , Deliu E , Dotter CP , et al. Impaired amino acid transport at the blood brain barrier is a cause of autism spectrum disorder[J]. Cell, 2016, 167 (6): 1481- 1494.e18.
doi: 10.1016/j.cell.2016.11.013
11 Smith AM , King JJ , West PR , et al. Amino acid dysregulation metabotypes: Potential biomarkers for diagnosis and individualized treatment for subtypes of autism spectrum disorder[J]. Biol Psychiatry, 2019, 85 (4): 345- 354.
doi: 10.1016/j.biopsych.2018.08.016
12 Sperringer JE , Addington A , Hutson SM . Branched-chain amino acids and brain metabolism[J]. Neurochem Res, 2017, 42 (6): 1697- 1709.
doi: 10.1007/s11064-017-2261-5
13 王强. Gesell发育量表对2岁以内孤独症谱系障碍(ASD)患儿的应用效果观察[J]. 世界最新医学信息文摘(连续型电子期刊), 2020, 20 (33): 61- 62.
14 Larsson SC , Markus HS . Branched-chain amino acids and Alzheimer's disease: A Mendelian randomization analysis[J]. Sci Rep, 2017, 7 (1): 13604.
doi: 10.1038/s41598-017-12931-1
15 Bjerkenstedt L , Edman G , Hagenfeldt L , et al. Plasma amino acids in relation to cerebrospinal fluid monoamine metabolites in schizophrenic patients and healthy controls[J]. Br J Psychiatry, 1985, 147, 276- 282.
doi: 10.1192/bjp.147.3.276
16 Tu WJ , Chen H , He J . Application of LC-MS/MS analysis of plasma amino acids profiles in children with autism[J]. J Clin Biochem Nutr, 2012, 51 (3): 248- 249.
17 Arnold GL , Hyman SL , Mooney RA , et al. Plasma amino acids profiles in children with autism: Potential risk of nutritional deficiencies[J]. J Autism Dev Disord, 2003, 33 (4): 449- 454.
doi: 10.1023/A:1025071014191
18 Witters P , Debbold E , Crivelly K , et al. Autism in patients with propionic academia[J]. Mol Genet Metab, 2016, 119 (4): 317- 321.
doi: 10.1016/j.ymgme.2016.10.009
19 Bala KA , Dǒgan M , Mutluer T , et al. Plasma amino acid profile in autism spectrum disorder (ASD)[J]. Eur Rev Med Pharmacol Sci, 2016, 20 (5): 923- 929.
20 Zou M , Li D , Wang L , et al. Identification of amino acid dys-regulation as a potential biomarker for autism spectrum disorder in China[J]. Neurotox Res, 2020, 38 (4): 992- 1000.
doi: 10.1007/s12640-020-00242-9
21 May T , Adesina I , McGillivray J , et al. Sex differences in neurodevelopmental disorders[J]. Curr Opin Neurol, 2019, 32 (4): 622- 626.
doi: 10.1097/WCO.0000000000000714
22 Lavelle A , Sokol H . Gut microbiota-derived metabolites as key actors in inflammatory bowel disease[J]. Nat Rev Gastroenterol Hepatol, 2020, 17 (4): 223- 237.
doi: 10.1038/s41575-019-0258-z
23 Lussu M , Noto A , Masili A , et al. The urinary (1) H-NMR metabolomics profile of an Italian autistic children population and their unaffected siblings[J]. Autism Res, 2017, 10 (6): 1058- 1066.
doi: 10.1002/aur.1748
24 Li C , Shen K , Chu L , et al. Decreased levels of urinary free amino acids in children with autism spectrum disorder[J]. J Clin Neurosci, 2018, 54, 45- 49.
doi: 10.1016/j.jocn.2018.05.001
25 Evans C , Dunstan RH , Rothkirch T , et al. Altered amino acid excretion in children with autism[J]. Nutr Neurosci, 2008, 11 (1): 9- 17.
doi: 10.1179/147683008X301360
26 De Angelis M , Piccolo M , Vannini L , et al. Fecal microbiota and metabolome of children with autism and pervasive developmental disorder not otherwise specified[J]. PLoS One, 2013, 8 (10): e76993.
doi: 10.1371/journal.pone.0076993
27 Carunchio I , Curcio L , Pieri M , et al. Increased levels of p70S6 phosphorylation in the G93A mouse model of amyotrophic lateral sclerosis and in valine-exposed cortical neurons in culture[J]. Exp Neurol, 2010, 226 (1): 218- 230.
doi: 10.1016/j.expneurol.2010.08.033
28 Nave KA , Werner HB . Myelination of the nervous system: Mechanisms and functions[J]. Annu Rev Cell Dev Biol, 2014, 30, 503- 533.
doi: 10.1146/annurev-cellbio-100913-013101
29 Kakazu E , Kanno N , Ueno Y , et al. Extracellular branched-chain amino acids, especially valine, regulate maturation and function of monocyte-derived dendritic cells[J]. J Immunol, 2007, 179 (10): 7137- 7146.
doi: 10.4049/jimmunol.179.10.7137
30 Shen L , Feng C , Zhang K , et al. Proteomics study of peripheral blood mononuclear cells (PBMCs) in autistic children[J]. Front Cell Neurosci, 2019, 13, 105.
31 Lungba RM , Khan S , Ajibawo-Aganbi U , et al. The role of the gut microbiota and the immune system in the development of autism[J]. Cureus, 2020, 12 (10): e11226.
32 Meltzer A , Van de Water J . The role of the immune system in autism spectrum disorder[J]. Neuropsychopharmacology, 2017, 42 (1): 284- 298.
doi: 10.1038/npp.2016.158
[1] Ya-nan ZHAO,Hui-yun FAN,Xiang-yu WANG,Ya-nan LUO,Rong ZHANG,Xiao-ying ZHENG. Early death and causes of death of patients with autism spectrum disorders: A systematic review [J]. Journal of Peking University (Health Sciences), 2023, 55(2): 375-383.
[2] JIAO Cui,WANG Jian-mei,KUANG Hai-xia,WU Zhi-hong,LIU Tao. Effects of CACNA1H gene knockout on autistic-like behaviors and the morphology of hippocampal neurons in mice [J]. Journal of Peking University (Health Sciences), 2022, 54(2): 209-216.
[3] SHI Hui-feng, ZHANG Jing-xu, ZHANG Rong, WANG Xiao-li. Prevalence of autism spectrum disorders in children aged 0-6 years in China: a meta-analysis [J]. Journal of Peking University(Health Sciences), 2017, 49(5): 798-806.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
No Suggested Reading articles found!
Copyright © Journal of Peking University (Health Sciences), All Rights Reserved.
Powered by Beijing Magtech Co. Ltd