The Role of Metal Ion Dyshomeostasis in ASD: Evaluation of Cu, Zn and Se Levels in the North American Autism Spectrum Disorder Population

Background: The importance of environmental factors and the extent of their role in the development of ASD are poorly understood. Zinc is a nutrient that may serve as a cofactor for 8 to 10% of currently identified autism risk genes. Previous studies have suggested that people on the autism spectrum have lower zinc and higher copper levels than control subjects. These studies also suggested a trend in which more severe symptoms of Autism were found in people with lower zinc levels. However, these studies were small and were performed in the Middle East or Asia. In addition, there are inconsistencies in the literature about the size of this effect depending on the source of the biosample (serum, hair, or nails).

Objectives: This study aims to determine whether the relationship between zinc/copper levels and ASD exists in a North American population and in a larger sample group size. Secondary aims of the study are to assess if there is a relationship between Zn/Cu/Se levels and language delay, functional level, and genotype. We also aim to determine if there is an optimal biosample to measure in this population based on effect size.

Methods: We are recruiting 100 children with ASD between ages 2 and 4 years and 50 age-matched control subjects from a tertiary care medical center. Control subjects passed standard pediatric screening for autism (the Ages and Stages Questionnaire), whereas all children with ASD were diagnosed using a multidisciplinary evaluation, including the ADOS-2. Zinc, copper, and selenium levels are measured in a CLIA-certified laboratory from serum, hair, and nail samples. All children diagnosed with ASD are offered clinical genetic testing (fragile X and chromosomal microarray). Once recruitment is complete, we will look for group differences between children with ASD and control subjects for zinc, copper, and selenium, as well as within ASD differences between metal ion levels and the severity of autism, language, and genetic diagnosis.

Results: Preliminary results indicated that there is a statistically significant difference between serum selenium levels, hair zinc levels, and the copper/zinc ratio between children with ASD and control subjects. There is not a high degree of concordance between metal ion levels across sample types for a given patient.

Conclusions: Our data suggest that there is a difference in metal ion homeostasis and absolute levels in young children with ASD and control subjects. We do not yet have sufficient power to determine whether there is a subtype of ASD or particular genetic diagnosis that accounts for most of this difference.