Evaluation of Zn, Cu, and Se Levels in the North American Autism Spectrum Disorder Population

Sunil Q Mehta,Lindsay R Stromback,Nicholas B Larson,Andrea R Huebner,Paul J Jannetto,Adriana M Delgado,Jessica M Davis,Patrick L Day,Timothy R Degrado,Flora Howie,Mukesh K Pandey,Supriya Behl

doi:10.3389/fnmol.2021.665686

Abstract

Metal ion dyshomeostasis and disparate levels of biometals like zinc (Zn), copper (Cu), and selenium (Se) have been implicated as a potential causative factor for Autism Spectrum Disorder (ASD). In this study, we have enrolled 129 children (aged 2–4 years) in North America, of which 64 children had a diagnosis of ASD and 65 were controls. Hair, nail, and blood samples were collected and quantitatively analyzed for Zn, Cu and Se using inductively coupled plasma mass spectrometry (ICP-MS). Of the analyzed biometals, serum Se (116.83 ± 14.84 ng/mL) was found to be significantly lower in male ASD cases compared to male healthy controls (128.21 ± 9.11 ng/mL; p < 0.005). A similar trend was found for nail Se levels in ASD (1.01 ± 0.15 mcg/g) versus that of controls (1.11 ± 0.17 mcg/g) with a p-value of 0.0132 using a stratified Wilcoxon rank sum testing. The level of Se in ASD cohort was co-analyzed for psychometric correlation and found a negative correlation between total ADOS score and serum Se levels. However, we did not observe any significant difference in Zn, Cu, and Zn/Cu ratio in ASD cases versus controls in this cohort of North American children. Further studies are recommended to better understand the biology of the relationship between Se and ASD status.

Highlights

Autism spectrum disorder (ASD) is a heterogeneous disorder characterized by both impaired social interaction, communication, and restricted, repetitive patterns in behavior (Lord et al, 2018)
Children aged 24–48 months newly diagnosed with Autism Spectrum Disorder (ASD) were recruited into the study from the Dana Neurodevelopmental Disorders program of Mayo Clinic (Rochester, Minnesota), along with age-matched controls seen in an outpatient community pediatrics clinic
The findings of this study indicate a significant association between lower Se levels and the presence of autism spectrum disorder

Summary

Introduction

Autism spectrum disorder (ASD) is a heterogeneous disorder characterized by both impaired social interaction, communication, and restricted, repetitive patterns in behavior (Lord et al, 2018). Genetic factors were predominantly implicated in ASD incidence. Hundreds of genes related to ASD incidence have been identified in the literature, ranging in relatedness and pathogenicity. Genetic influence over ASD is heterogeneous and is seen in the form of rare chromosomal variants to common single nucleotide polymorphisms. Genes associated with ASD tend to peak in transcription during early fetal development, around the second trimester (Parikshak et al, 2013; Willsey et al, 2013). While this information may be clinically relevant (Vorstman et al, 2017), genetic variants only account for a portion of ASD susceptibility (Tick et al, 2016)

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Conclusion