Leucovorin Therapy in Children with Autism and Elevated B12 Levels

Assessment and Precautions

Evaluate the cause of elevated B12 (>2000) to identify potential underlying metabolic issues or supplementation, as recommended by the American Academy of Pediatrics 1
Assess iron status, including total iron binding capacity and ferritin levels, to investigate possible iron metabolism issues 3
Measure methylmalonic acid and homocysteine levels to assess functional B12 status, as these markers are more sensitive than serum B12 alone 4
The American Academy of Pediatrics recommends testing for folate receptor autoantibodies (FRAA) and genetic testing for MTHFR and other folate metabolism pathway variants to guide leucovorin therapy 1, 2

Leucovorin (folinic acid) is used to bypass potential folate metabolism issues and improve cerebral folate status in children with autism, as supported by the National Comprehensive Cancer Network 1, 7
Leucovorin does not require the same metabolic conversion as folic acid and may be more bioavailable to the brain, according to the Clinical Nutrition guidelines 2, 7

Start with a low dose of leucovorin (approximately 5 mg/day) and gradually increase while monitoring for side effects, as recommended by the Pediatrics guidelines 1
Monitor for potential interactions with current medications and adjust dosing based on clinical response and follow-up lab values, including B12, folate, homocysteine, and methylmalonic acid levels 5, 6, 7
Recheck lab values after 3 months of treatment and assess for clinical improvements in autism symptoms and potential adverse effects, particularly in patients with abnormal liver or kidney function 1, 5, 6