An Examination of Changes in Urinary Metabolites and Behaviors with the Use of Leucovorin Calcium in Children with Autism Spectrum Disorder (ASD)

Abstract

Children with autism spectrum disorder (ASD) have been found to have a high prevalence of folate receptor auto-antibodies (FRAA), which may impair the normal transport of folate from blood into the cerebrospinal fluid (CSF). Leucovorin calcium (LC) is believed to bypass the folate transport system and restore function. We sought to examine changes in behavior and urinary metabolites in children and young adults with ASD being treated with LC. Students attending a K-12 school for ASD were recruited for an open-label, 12-week study of high-dose LC (2 mg/kg/day, max dose 50 mg/day). The primary outcome measures were the mean changes in the Aberrant Behavior Checklist (ABC) and the Social Responsiveness Scale (SRS). We also examined changes in Pediatric Quality of Life (PedsQL) and urinary metabolites. Changes were assessed with paired sample t-tests. Twelve students aged 13 to 19 (2 girls, 10 boys) completed the study. The parent-reported SRS showed a non-significant decrease (improvement) of 7.8 points (95% CI − 1.6 to 17.3, p = 0.095), and the ABC showed a non-significant decrease of 2.4 points (95% CI − 6.4 to 11.3, p = 0.56). The teacher-reported ABC and the parent-reported PedsQL showed very little change. Urinary metabolites with the greatest changes were involved in folate, phosphatidylcholine, and tocopherol metabolism. In an open-label study of school-aged children with ASD, LC treatment did not lead to significant improvements. The parent-reported SRS showed a non-significant improvement of 7.8 points, which is clinically important and worthy of future study with larger samples. The potential benefits of LC may be limited to children with a specific physiological abnormality (e.g., FRAA status) and may require a targeted treatment approach. Urinary metabolites may be a useful tool to identify children who are likely to respond to treatment.