Classification of Autism Spectrum Disorder from Blood Metabolites: Robustness to the Presence of Co-occurring Conditions

Background: Previous studies have found plasma measurements of metabolites from the folate dependent one-carbon metabolism (FOCM) and transsulfuration (TS) pathways to be useful for differentiating individuals with autism spectrum disorder (ASD) from their typically developing peers. ASD is heterogeneous due to wide variation in the presence of co-occurring behavioral and medical conditions, and it is unknown how these conditions influence the ability to identify ASD based on FOCM/TS metabolites.

Method: This study employs a previously developed multivariate model that makes use of five FOCM/TS measurements (S-adenosylmethionine/S-adenosylhomocysteine, glutamylcysteine, glutathione disulfide, free cystine/free cysteine, and percent oxidized glutathione) to distinguish children with ASD from typically developing children. The model is used here to evaluate an independent cohort of individuals having ASD with diagnosed co-occurring conditions (age range 2 – 17 years old) and assess classifier performance in the presence/absence of these conditions. The four categories of co-occurring conditions considered were allergic disorders, gastrointestinal disorders, immune/metabolic disorders, and neurological disorders. All data were collected and retrospectively analyzed from previous clinical studies.

Results: The model was able to identify 124 of 131 participants with ASD (94.7%) correctly regardless of co-occurring condition status. Model performance was generally not sensitive to the absence or presence of most co-occurring conditions, with the exceptions of ever/never having allergies or gastrointestinal symptoms, or currently (not) having any condition, all of which had minor impacts on model prediction accuracy.

Conclusion: The results of this exploratory study suggest that a FOCM/TS-based classifier for diagnosing ASD may potentially be robust to variations in co-occurring conditions and potentially applicable across ASD subtypes. Larger, more comprehensive follow-up studies with typically developing and/or developmentally delayed control groups are required to provide a more conclusive assessment of classifier robustness to co-occurring conditions.