MTHFS and hyperinsulinemic hypoglycemia, familial, 4: Fourth, MTHFS deficiency also exhibits an intramitochondrial folate deficiency, which would shunt intramitochondrial translation of mitochondrial methionyl-tRNA and lead to secondary mitochondrial dysfunction, resulting in deficient energy for brain development (Bertrand et al., 1995; Fox and Stover, 2008; Wang et al., 2021).