Management of neonatal MTHFR mutation with hyperhomocysteinemia presenting as apnea and encephalopathy requires prompt metabolic and supportive treatment. The current regimen you described—methylfolate, hydroxocobalamin (B12), pyridoxine (B6), betaine, choline, and carnitine—is appropriate and targets reduction of homocysteine levels by supporting remethylation and transsulfuration pathways.

Key points:

• Betaine acts as a methyl donor, lowering homocysteine effectively.
• Pyridoxine is vital for the transsulfuration pathway to convert homocysteine to cystathionine.
• Regular monitoring of plasma homocysteine and methionine levels is essential.
• Supportive care for apnea and encephalopathy is critical, including respiratory support as needed.
• Early diagnosis and treatment can improve neurological outcomes, but prognosis varies.

For refractory or severe cases, consultation with a metabolic specialist and consideration of additional therapies such as folinic acid or specialized diets may be needed.

Reference: Mudd, S. H., et al. (2001). Homocysteine and related disorders. In The Metabolic and Molecular Bases of Inherited Disease, 8th ed. McGraw-Hill. https://www.ncbi.nlm.nih.gov/books/NBK1191