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 mcg/mL) was found to be significantly lower in male ASD cases compared to male healthy controls (128.21 ± 9.11 mcg/mL; p < 0.005). A similar trend was found for nail Se levels in ASD (1.01 ± 0.15 mcg/mL) versus that of controls (1.11 ± 0.17 mcg/mL) 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.
Background Gadolinium-based contrast agents (GBCAs) have been used in magnetic resonance imaging for the past 30 years, where they have significantly improved the effectiveness of imaging studies. However, the increased usage of gadolinium in the medical community has also resulted in unexpected interferences in other laboratory assays. This has been particularly the case in clinical elemental analysis using inductively coupled plasma mass spectrometry (ICP-MS). Methods By conducting ICP-MS interference experiments, we describe how gadolinium interferes with elemental analysis by space charge effect, double charge effect and the creation of polyatomic interferences. Additionally, by reviewing more than a year of reference laboratory data from our laboratory information system, we determined the number of elemental tests cancelled due to gadolinium interference. Results Interference experiments show that gadolinium normally found in GBCAs can interfere with heavy metals, platinum and selenium analysis of biological fluids using ICP-MS. Within one year, our institution’s metals laboratory had to cancel 42 selenium serum tests and 19 heavy metal urine panels due to potential interference caused by gadolinium. Conclusions GBCAs will continue to be utilized in hospitals around the world. However, clinical laboratories should be wary of potential interferences caused by GBCAs. Relevant interferences include space charge effect, double charge interference, and the formation of polyatomic interferences caused by gadolinium. These interferences can negatively affect patient care by resulting in cancelled laboratory tests and causing patients to have blood redrawn and analysed at a later date leading to delays in their diagnosis/treatment.
To better understand zinc and copper regulation and their involvement in various biochemical pathways as it relates to autism spectrum disorder (ASD), isotopic composition of serum zinc and copper were evaluated in both healthy children and children with ASD in North America. No significant difference in isotopic composition of serum zinc or copper with respect to healthy controls and ASD children were identified. However, the isotopic composition of serum copper in boys was found to be enriched in 65Cu in comparison to previously published healthy adult copper isotopic composition. Furthermore, in both boys and girls, the average isotopic composition of serum zinc is heavier than previously published healthy adult isotopic zinc composition. There was also a negative association between total zinc concentrations in serum and the zinc isotopic composition of serum in boys. Finally, children with heavier isotopic composition of copper also showed a high degree of variability in their zinc isotopic composition. While numerous studies have measured the isotopic composition of serum zinc and copper in adults, this is one of the first studies which measured the isotopic composition of serum copper and zinc in children, specifically those diagnosed with ASD. The results of this study showed that age and gender specific normal ranges of isotopic composition must be established to effectively use isotopic composition analysis in studying various diseases including ASD.
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