A 4-year-old child presents with developmental delay, seizures, and homocysteine elevation in blood. Urine homocystine is positive. Plasma methionine is low-normal. MTHFR activity in fibroblasts is markedly reduced. Which cofactor supplementation is most likely to be beneficial?
- A Folinic acid (5-formyl-THF) ✓
- B Pyridoxine (B6)
- C Cobalamin (B12)
- D Biotin
Correct answer: A. Folinic acid (5-formyl-THF)
Explanation
MTHFR deficiency impairs conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, the methyl donor for homocysteine remethylation to methionine. Folinic acid (5-formyl-THF) can bypass this block by entering the folate cycle upstream. Pyridoxine helps in CBS deficiency. B12 helps in cobalamin C/D defects. This is distinct from CBS deficiency where methionine is elevated, not low-normal.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.