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Given that some mutant enzymes retain low-level FAD-binding capacity, a gene + high-dose riboflavin synergy strategy has been proposed: in AIFM1 encephalopathies, low-level AAV transduction re-establishes baseline protein expression, while daily riboflavin doses above 400 mg act as a molecular chaperone to stabilize FAD binding a regimen shown to improve ICARS scores and neuroimaging outcomes (75)

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While the etiology of NTD is multifactorial, some studies have found that blood concentrations of homocysteine or holo-transcobalamin to be lower in NTD-affected infants and mothers compared to non-affected controls (reviewed in 59)

Any visible bits, flecks, or debris mean it is time to discard the vial