What is the next course of action before safely starting Leucovorin (folinic acid) in a patient with elevated B12 levels, low total iron binding capacity, and normal complete blood count (CBC), homocysteine, methylmalonic acid (MMA), iron, and ferritin levels, without a cerebrospinal fluid (CSF) sample?

Next Steps Before Starting Leucovorin in a Child with Autism and Elevated B12 Levels

Before safely starting leucovorin (folinic acid) in this nearly 4-year-old child with autism and abnormal lab values, you should first rule out potential causes of the elevated B12 level (>2000) and evaluate folate metabolism through additional testing.

Assessment of Elevated B12 and Iron Status

• Evaluate the cause of elevated B12 (>2000) as this may indicate underlying metabolic issues or supplementation 1
• Assess if the child is currently taking any B12 supplements or multivitamins that could explain the elevated levels 1
• The low total iron binding capacity (9) with normal ferritin (>20) suggests possible iron metabolism issues that should be further investigated 1
• Consider measuring methylmalonic acid and homocysteine levels, which are more sensitive markers of functional B12 status than serum B12 alone 1

Additional Testing Before Starting Leucovorin

• Measure serum folate to assess current folate status 1
• Test for folate receptor autoantibodies (FRAA) which are common in autism and may indicate a need for leucovorin 1
• Consider genetic testing for MTHFR and other folate metabolism pathway variants 1
• Assess liver function tests as abnormalities may require caution with leucovorin 1

Rationale for Leucovorin Use in Autism

• Leucovorin (folinic acid) is used in autism to bypass potential folate metabolism issues and improve cerebral folate status 1
• Unlike folic acid, leucovorin does not require the same metabolic conversion and may be more bioavailable to the brain 1
• Leucovorin can help normalize homocysteine levels in patients with elevated B12, which is important as hyperhomocysteinemia has been linked to neurological issues 1

Dosing Considerations

• Start with a low dose of leucovorin (approximately 5 mg/day) and gradually increase while monitoring for side effects 1
• Dosing may need to be adjusted based on clinical response and follow-up lab values 1
• Monitor for potential interactions with any current medications the child may be taking 1

Follow-up Monitoring

• Recheck B12, folate, homocysteine, and methylmalonic acid levels after 3 months of treatment 1
• Monitor for clinical improvements in autism symptoms 1
• Assess for any adverse effects, particularly if the child has abnormal liver or kidney function 1

Important Precautions

• Avoid starting leucovorin without ruling out potential metabolic disorders that could be masked by treatment 1
• Be aware that leucovorin does not cross the blood-brain barrier in amounts sufficient to interfere with methotrexate in CSF, but this is not relevant for autism treatment 1
• The elevated B12 with normal homocysteine and MMA suggests a functional B12 status that needs to be understood before adding leucovorin 1

Remember that while CSF analysis would be ideal to assess cerebral folate status, the additional testing recommended above provides a reasonable alternative when CSF sampling is not feasible in this pediatric patient.