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ORIGINAL ARTICLE
Year : 2022  |  Volume : 35  |  Issue : 1  |  Page : 116-119

Study of trace elements and electrolytes in autism spectrum disorder in an Egyptian children sample


1 Department of Neuropsychiatry, Faculty of Medicine, Menoufia University, Menoufia, Egypt
2 Department of Neuropsychiatry, Sadat City General Hospital, Menoufia, Egypt

Date of Submission09-Oct-2020
Date of Decision02-Feb-2021
Date of Acceptance08-Feb-2021
Date of Web Publication18-Apr-2022

Correspondence Address:
Amira A AbdElhalim Othman
Department of Neuropsychiatry, Sadat City General Hospital, Mohafazet, Menoufia 32958
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mmj.mmj_348_20

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  Abstract 


Objective
To Assess serum trace elements and electrolytes in Egyptian children with autism.
Background
The relationship between plasma levels of trace elements in patients with autism spectrum disorder (ASD) has polarized the interest of many physiologists in recent years owing to the evidence that the impaired homeostatic regulation of trace elements, their levels in the bloodstream, and their potential neurotoxicity, altogether contribute to the ASD etiology.
Patients and methods
It is a cross-sectional study. The study was conducted on 60 children aged 3–12 years old, both sexes, and all social classes.
Results
The study showed a highly significant decrease in serum zinc in patient sample, which was 75.53 ± 18.585, in comparison with the control sample, which was 106.27 ± 14.714. It is highly significant, P value is less than 0.001. There was a highly significant difference between zinc/copper ratio and copper/zinc ratio. Zinc/copper ratio of patient was 0.5747 ± 0.14793, whereas for control was 0.9233 ± 0.18102 with P value less than 0.001. Copper/zinc ratio of patients was 1.8433 ± 0.45360, whereas the ratio for the controls was 1.0980 ± 0.17993, with P value less than 0.001. Our study showed that there were no significant differences in serum level of iron, magnesium, sodium, potassium, and calcium, as well as copper between ASD and control groups.
Conclusion
The study showed a highly significant decrease in serum zinc between ASD and control groups. There was a highly significant difference between zinc/copper ratio and copper/zinc ratio. There was a highly significant difference regarding zinc/copper ratio between ASD and control groups. There was no significant difference in serum level of copper, iron, magnesium, sodium, potassium, and calcium between ASD and control.

Keywords: autism spectrum disorder, copper, electrolytes, trace elements, zinc


How to cite this article:
Al Hadad AA, Ramadan AN, Othman AA. Study of trace elements and electrolytes in autism spectrum disorder in an Egyptian children sample. Menoufia Med J 2022;35:116-9

How to cite this URL:
Al Hadad AA, Ramadan AN, Othman AA. Study of trace elements and electrolytes in autism spectrum disorder in an Egyptian children sample. Menoufia Med J [serial online] 2022 [cited 2024 Mar 28];35:116-9. Available from: http://www.mmj.eg.net/text.asp?2022/35/1/116/343118




  Introduction Top


Autism spectrum disorder (ASD) describes a wide range of symptoms, including difficulty with social interaction and communication skills, as well as unusually repetitive behavior [1]. Although the exact cause of ASD is still not known, it is believed that both genetic and environmental factors influence the onset and development of this disorder. Interaction between multiple genetic variants and epigenetic factors also increase the risk of having ASD [2]. Trace elements are essential for many physiological functions, as they act as a cofactor in various enzymatic processes, and hence their biochemical regulation is of major importance [3]. The plasma concentration of these elements may be affected by different habits in the dietary intake, by environmental factors, and other ones that can play a role in the pathophysiology of ASD [4].

The relationship between plasma levels of trace elements in patients with ASD has polarized the interest of many physiologists in recent years owing to the evidence that the impaired homeostatic regulation of trace elements, their levels in the bloodstream, and their potential neurotoxicity, altogether contribute to the ASD etiology [5]. We designed this study to assess serum trace elements and electrolytes in Egyptian children with autism and study their role in the etiology of autism.


  Patients and methods Top


The study was conducted 60 children aged 3–12 years old, both sexes and all social classes. They were recruited from the neuropsychiatric outpatient clinic of the Faculty of Medicine, Menoufia University, and neuropsychiatric outpatient clinic in Sadat General Hospital in Sadat City.

The patients in this study were divided into two groups.

Patient group consisted of 30 children with ASD, and control group included 30 neurotypically developed healthy children.

Inclusion criteria (for patient group)

Both sexes, age from 3 to 12 years old, all socioeconomic classes, autistic children who met the Diagnostic and Statistical Manual of Mental Disorders-5 criteria for ASD, and whose score was more than or equal to 30 according to CARS II were the inclusion criteria.

Exclusion criteria

Any child whose parents refused consent, any child with comorbid psychiatric or medical illness, any child with any organic brain lesion or significant head trauma, any child with metal implants, any child who uses dietary mineral supplements or mineral-containing shampoos, and vegetarianism were excluded.

Methods

All study procedures were approved by the ethical committee. Informal consent from parents or legal guardians of participants was obtained after the nature of procedures had been fully explained. The interviews were conducted with mothers in 83% of the cases and with both parents in 17% of cases.

Each child was subjected to the following.

Careful history taking using sociodemographic data sheet

It consists of information about the name, age, and sex of the patient. In addition, there were other data for assessing the socioeconomic class of the child derived from Fahmy and El-Sherbini scale for social classification. It is an Egyptian scale that includes mothers' and fathers' education and occupation, number of bedrooms, and family income.

Clinical psychiatric interview included general, neurological examination, and Diagnostic and Statistical Manual of Mental Disorders-5 diagnostic criteria for ASD.

CARS II was evaluated in children with clinical signs of ASD to confirm the diagnosis.

Sample collection and trace element measurements

Whole blood samples were obtained from all examined children by using 4-ml lithium heparin vacuum blood collection tubes (20 international unit lithium heparin/ml). Before measurements, 40 μl whole blood of each sample was added into 1-ml sample diluent, which was individually packed, and then they were mixed by vibration. The obtained samples from cases and controls were used for chemical analysis for trace elements, including zinc, copper, and iron, and serum electrolytes, including sodium, potassium, calcium, and magnesium.

The quantitative analyses of trace element contents were performed by using flame atomic absorption spectroscopy on a multichannel atomic absorption spectrophotometer.

Statistical analysis

Data collected through history, basic clinical examination, laboratory investigations, and outcome measures were coded, entered, and analyzed using Microsoft Excel software. Data were then imported into the Statistical Package for the Social Sciences (SPSS, version 23.0) (SPSS Inc., Chicago, Illinois, USA). software for analysis. According to the type of data, the following tests were used to test differences for significance.

Two types of statistics were done:

Descriptive statistics: for example, percentage (%), mean, and SD.

Analytical statistics included the following:

χ2) was used to study association between two qualitative variables.

Student t test was a test of significance used for comparison between two groups having normally distributed quantitative variables.

P value less than or equal to 0.05 is considered significant.

P value less than 0.001 is considered highly significant.

All study procedures were approved by the local research ethics committee of Menoufia University. Informal consent from parents or legal guardians of participants was obtained after the nature of procedures had been fully explained. The interviews were conducted with mothers in 83% of the cases and with both parents in 17% of cases.


  Results Top


The study was conducted on 60 children aged 3–12 years old, of both sexes and all social classes. There were 30 children with ASD, with mean age of 7.20 ± 2.007 years, comprising 22 males and eight females. Moreover, 30 normal control children were included, with mean age of 7.13 ± 2.615 years [Table 1].
Table 1: Sociodemographic data of the case and control groups

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Our study showed a highly significant decrease in serum zinc in the patient sample, representing 75.53 ± 18.585, in comparison with the control sample, representing 106.27 ± 14.714. It is highly significant, as P value is less than 0.001 [Table 2].
Table 2: Comparison between case and control groups in the result of serum zinc, serum copper, serum iron, serum sodium, serum potassium, serum magnesium, and serum calcium

Click here to view


Our study showed no significant differences between patients and controls regarding serum copper, as serum copper in patient was 133.80 ± 23.349 and in controls was 117.13 ± 27.292, with P value more than 0.05 [Table 2].

Our study showed a highly significant difference between zinc/copper ratio and copper/zinc ratio. Zinc/copper ratio of patient was 0.5747 ± 0.14793, whereas for control was 0.9233 ± 0.18102, with P value less than 0.001. Copper/zinc ratio of patients was 1.8433 ± 0.45360, whereas for the control was 1.0980 ± 0.17993, with P value less than 0.001 [Table 3].
Table 3: Comparison between case and control groups in the results of zinc/copper ratio and copper/zinc ratio

Click here to view


Our study reported there was no significant differences in serum level of iron, magnesium, sodium, potassium, and calcium between ASD and control groups [Table 2].


  Discussion Top


The study was done to shed a spot of light on the role of trace elements and electrolytes in ASD in Egyptian children sample.

The ASD describes a wide range of symptoms, including difficulty with social interaction and communication skills, as well as unusually repetitive behavior [1].

The obtained data reported a significant alteration of some trace element status in children with ASD. The most prominent changes in essential trace elements status in autistic children were detected for zinc/copper ratio.

Our results are in disagreement with Skalny et al. [6], who showed that there was no significant change in zinc in patients than controls.

Zinc is involved in different dimensions of neural development, for example neurogenesis, neuronal migration, differentiation, and apoptosis. Therefore, zinc deficiency can affect both prenatal and postnatal life, thereby causing serious neurological complications, mainly neurodevelopmental problems [7],[8]. It has also shown anti-inflammatory and antioxidative effects[9] to the extent that zinc deficiency is considered a common type of nutritional immunodeficiency [10]. Accordingly, its deficiency may make individuals vulnerable to inflammatory and other immune abnormalities, importantly infections (pneumonia) and autoimmune disorders (inflammatory bowel disease) [11],[12],[13]. Zinc deficiency is predominantly seen among people who live in developing countries, elderly people, and patients with nutritional dwarfism [14],[15],[16].

Consistent with our results Skalny et al.[6] and Crăciun et al.[17] reported that there was no significant increase in copper in children with ASD. Crăciun et al.[17] reported that there was a significant increase in cooper/zinc ratio and significant decrease in zinc/copper ratio.

Consistent with our results, Macedoni-Lukšič et al.[18] reported that there was a significant increase in copper/zinc ratio [18].

Our results come in line with a study done by Skalny et al. [6], who reported that there were no significant differences in serum level of iron, magnesium, sodium, potassium, and calcium between ASD and control groups.

On the contrary, our results are in disagreement with El-Ansary and Al-Ayadhi [19], who reported that there was significant alteration of iron, magnesium, sodium, potassium, and calcium between ASD and control groups.


  Conclusions Top


Our study showed a highly significant decrease in serum zinc between ASD and control. Our study showed there was a highly significant difference between zinc/copper ratio and copper/zinc ratio. There was a highly significant difference regarding zinc/copper ratio between ASD and control. Our study showed no significant differences in serum level of iron, magnesium, sodium, potassium, and calcium between ASD and control groups.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders: DSM-5®, American Psychiatric Association, Washington, 2013.  Back to cited text no. 1
    
2.
Tordjman S, Somogyi E, Coulon N, Kermarrec S, Cohen D, Bronsard G, et al. Gene × environment interactions in autism spectrum disorders: role of epigenetic mechanisms. Front Psychiatry 2014; 5:53.  Back to cited text no. 2
    
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Zhang Y. Trace elements and healthcare: a bioinformatics perspective. Adv Exp Med Biol 2017; 1005:63–98.  Back to cited text no. 3
    
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Saghazadeh A, Rezaei N. Brain-derived neurotrophic factor levels in autism: a systematic review and meta-analysis. J Autism Dev Disord 2017; 47:1018–1029.  Back to cited text no. 4
    
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Grabrucker S, Jannetti L, Eckert M, Gaub S, Chhabra R, Pfaender S, et al. Zinc deficiency dysregulates the synaptic ProSAP/Shank scaffold and might contribute to autism spectrum disorders. Brain 2014; 137(Pt 1):137–152.  Back to cited text no. 5
    
6.
Skalny AV, Simashkova NV, Klyushnik TP, Grabeklis AR, Radysh IV, Skalnaya MG, et al. Assessment of serum trace elements and electrolytes in children with childhood and atypical autism. J Trace Elem Med Biol 2017; 43:9–14.  Back to cited text no. 6
    
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Hambidge M. Human zinc deficiency. J Nutr 2000; 130 (5S Suppl):1344S–1349SS.  Back to cited text no. 7
    
8.
Uriu-Adams JY, Keen CL. Zinc and reproduction: effects of zinc deficiency on prenatal and early postnatal development. Birth Defects Res B Dev Reprod Toxicol 2010; 89:313–325.  Back to cited text no. 8
    
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Prasad AS. Zinc: role in immunity, oxidative stress and chronic inflammation. Curr Opin Clin Nutr Metab Care 2009; 12:646–652.  Back to cited text no. 9
    
10.
Fraker PJ. Zinc deficiency: a common immunodeficiency state. Surv Immunol Res 1983; 2:155–163.  Back to cited text no. 10
    
11.
Kristy M, Hendricks RD, DSc W, Allan Walker MD. Zinc deficiency in inflammatory bowel disease. Nutr Rev 1988; 46:401–408.  Back to cited text no. 11
    
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Shankar AH, Prasad AS. Zinc and immune function: the biological basis of altered resistance to infection. Am J Clin Nutr 1998; 68 (2 Suppl):447S–463S.  Back to cited text no. 12
    
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Black MM. Effects of vitamin B12 and folate deficiency on brain development in children. Food Nutr Bull 2008; 29 (2 Suppl):S126–S131.  Back to cited text no. 13
    
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Prasad AS, Miale AJR, Farid Z, Sandstead HH, Schulert AR. Zinc metabolism in patients with the syndrome of iron deficiency anemia, hepatosplenomegaly, dwarfism, and hypognadism. J Lab Clin Med 1963; 61:537–549.  Back to cited text no. 14
    
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Halsted JA, Ronaghy HA, Abadi P, Haghshenass M, Amirhakemi GH, Barakat RM et al. Zinc deficiency in man: the Shiraz experiment. Am J Med 1972; 53:277–284.  Back to cited text no. 15
    
16.
Prasad AS, Fitzgerald JT, Hess JW, Kaplan J, Pelen F, Dardenne M. Zinc deficiency in elderly patients. Nutrition 1993; 9:218–224.  Back to cited text no. 16
    
17.
Crăciun EC, Bjørklund G, Tinkov AA, Urbina MA, Skalny AV, Rad F, et al. Evaluation of whole blood zinc and copper levels in children with autism spectrum disorder. Metab Brain Dis 2016; 31:887–890.  Back to cited text no. 17
    
18.
Macedoni-Lukšič M, Gosar D, Bjørklund G, Oražem J, Kodrič J, Lešnik-Musek P, et al. Levels of metals in the blood and specific porphyrins in the urine in children with autism spectrum disorders. Biol Trace Elem Res 2015; 163:2–10.  Back to cited text no. 18
    
19.
El-Ansary A, Al-Ayadhi L. GABAergic/glutamatergic imbalance relative to excessive neuroinflammation in autism spectrum disorders. J Neuroinflammation 2014; 11:189.  Back to cited text no. 19
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

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