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. 2023 Jan 18;54(4):1567–1581. doi: 10.1007/s10803-022-05829-z

Table 5.

Comparison of case-control studies of plasma amino acids in children with ASD

Author (country/region; race; publication year; journal) ASD group n(male/female;age(M ± SD) Control group n(male/female;age(M ± SD) Diagnostic criteria(ASD) Types of Sample Detection method amino acids (AAs) outcomes Cognition(DQ/IQ) Severity of autism Regression Others

1. Adams JB et al.

(America/Arizona; Nil; 2011; Nutrition & Metabolism)

 55(49/6; 10 ± 3.1y) 44(39/5; 11 ± 3.1y) DSM-IV Plasma HPLC-MS/MS

Forty one plasma AAs measured.

1. ASD group:

1) Increased level: glutamate, serine, beta-amino isobutyrate, and homocysteine.

2) Decreased level: tryptophan, isoleucine, phenylalanine, tyrosine, and taurine.

2. Severity of autism:

The proline, serine, ethanolamine, or beta-amino-isobutyrate correlated with the severity of autism for all three scales (PDD-BI/ATEC/SAS).

 Nil PDD-BI/ATEC/SAS Nil

1. Fasting for 8-12 h.

2. Sex-age matched.

3. Children’ age 5–16 years old in both groups.

4. No usage of a vitamin/mineral supplement in the last 2 Mo.

5. No current use of any chelation treatment.

6. 20 out of 41 plasma AAs below the detection limit.
2. Naushad SM et al. (India/Hyderabad; Nil;2013; Indian Journal of Biochemistry & Biophysis) 138(120/18; 4.4 ± 1.7y) 138(120/18; 4.4 ± 1.6y) DSM-IV/ABC Plasma Reverse-phase HPLC

Ten plasma AAs tested.

ASD group:

1) Increased level: glutamate, and asparagine.

2) Decreased: tryptophan, histidine, methionine, and phenylalanine.

 DQ (ASD group: 30 < DQ < 80/control group: DQ > 80) Nil Nil

1. No special diet during the time of analysis.

2. Fasting blood samples.

3. ABC score:

ASD group >68 score; Control group<21score.

4. Sex-age matched.
3. Cai J et al. (China /Shangdong; Han; 2016;NeuroReport) 51(42/9; average age:3.69y)

Healthy control: 51(42/9; average age :3.69y);

ID group: 51(42/9; average age :3.69y)

 DSM-IV Plasma LC-MS/MS

Only detected glutamate.

1. ASD group:

Increased level: glutamate.

2. Severity of autism:

The increased level of glutamate positively associated with severity of autism.

Average FSIQ (ASD /control/ID group): 72.6/102

/68.7

 Average CARS score (ASD/control/ID group): 41.1/21.8 /22.5 Nil

1. Medication free for at least 5 weeks.

2. BMI (ASD/Control/ID group):16.3/17.2/17 Kg/m2.
4. Vargason T et al. (America/Arizona: Caucasian; 2018: Research Autism Spectrum Disorder)

64 (52/12;

11.8 ± 8.5y)

49 (40/9;

12.2 ± 7.6y)

 ADOS/CARS Plasma GC/MS

Twenty two plasma AAs and related amino acid metabolites were measured.

ASD group:

Increased level: glutamate, serine and hydroxyproline.

RIAS:

assess the IQ of ASD group children

 CARS Nil

1. Fasting overnight.

2. Age-sex matched.

3. ASD group: (45 children, 13 teens, 6 adults); Control group: (34 children, 10 teens, 5 adults).

4. 20 out of plasma AAs excluded for final analysis because of below the detection limit.
5. Zou M et al. (China/Harbin; Han; 2020;Neurotox Research) 70 (62/8; 5.44 ± 1.36y) 70 (62/8; 5.12 ± 0.79y) DSM-5 Plasma LC-MS/MS

Twenty one plasma AAs measured.

1. ASD group:

Increased level:

Arginine, cysteine, homocysteine, histidine, methionine, serine, tyrosine and valine.

2. Severity of autism: The level of homocysteine was positively correlated with the severity of autism.

 Nil ADOS-CSS Nil

1. Standardized diet and moderate physical activity for one week.

2. Fasting blood samples.
6. Xing Y et al. (China /Guangzhou; Han; 2021; Psychiatry Research) 60(49/11; 42.86 ± 11.03Mo) 30(25/5; 39.32 ± 12.88Mo) DSM-IV Serum TMS

Twenty two serum AAs measured.

1. ASD group:

1) Increased level: asparagine.

2) Decreased level: lysine, tryptophan, phenylalanine, methionine, leucine, valine, threonine, glutamine, glycine, alanine, citrulline, cysteine, serine, tyrosine acid, and proline.

2. The serum glutamate/glutamine (Glu/Gln) ratio was elevated in the ASD PIQ ≥ 70 group.

ASD group:

15 out of 60 children

(3y and11Mo): assessed with C-WYCSI(FIQ: 48.0 ± 18.7; VIQ: 46.4 ± 12.9; PIQ: 58.8 ± 22.4).

 Nil Nil

1. BMI for each child.

2. Fast for 10 h.
7. Current research

110(95/15;

3.22 ± 1.18y)

55(45/10;

3.37 ± 1.23y)

 DSM-5/ADI-R/ADOS Plasma LC-MS/MS

Forty eight plasma AAs measured and 43 plasma AAs analyzed.

1. ASD group:

1) Elevated level: glutamate, γ-Amino-n-butyric acid, glutamine, sarcosine, δ-Aminolevulinic acid, glycine and citrulline.

2) Decreased level: ethanolamine, phenylalanine, tryptophan, homocysteine, pyroglutamic acid, hydroxyproline, ornithine, histidine, lysine, and glutathione.

2. Severity of autism: The level of tryptophan distinct lower in severe group than in mild and moderate group.

DQ/IQ: by GDDS/WISC-I V/WPPSI-IV):

HFG:

DQ/IQ ≥ 70 ;LFG: (DQ/IQ < 70)

CARS:

Severe autism: CARS score ≥ 36.5;

mild and moderate autism:

30 ≤ CARS socre < 36.5

 ASD group: Regressive group and Non-regressive group

1. Fasting for 5-10 h.

2. Excluded vitamin B12 deficiency.

3. Age-sex matched.

4. 5 out of forty eight plasma AAs excluded due to below the detection limit.

ABC: Autism Behavior Scale; ADI-R: Autism Diagnostic Interview Revised; ADOS: Autism Diagnostic Observation Scale; ASD: Autism Spectrum Disorder; ATEC : Autism Evaluation Treatment Checklist; BMI: Body Mass Index; CARS: Childhood Autism Rating Scale; CSS: Calibration Severity Score; C-WYCSI: Chinese-Wechsler Young Children Scale of Intelligence; DQ: Development Quotient; DSM-IV: Diagnostic and Statistical Manual of Mental Disorders-IV; DSM-5: Diagnostic and Statistical Manual of Mental Disorders-5; FSIQ: Full Scale Intelligence Quotient; GC/MS: Gas Chromatography/Mass Spectrometry; GDDS: Gesell Development Diagnosis Scale; h: hour; HFG: High Functional Group; HPLC: High Performance Liquid Chromatography; ID: Intellectual Disability; LC-MS/MS: Liquid Chromatography-Tandem Mass Spectrometry; LFG: Low Functional Group; M: Mean; Mo: Month; PDD-BI: Pervasive Development Disorder-Behavior Inventory; PIQ: Performance Intelligence Quotient; RIAS: Reynolds Intelligence Assessment Scale; SAS: Severity of Autism Scale; SD: Standard Deviation; TMS:: Tandem Mass Spectrometry; VIQ: Verbal Intelligence Quotient; WISC-IV: Wechsler Intelligence Scale for Children-IV; WPPSI-IV: Wechsler Preschool and Primary Scale of Intelligence-IV; y: year