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Interestingly, the age-dependent decrease in methionine synthase, the target of mB12 in the methionine pathway, may be accelerated in the ASD brain (Muratore et al., As has been summarized previously, early studies in ASD demonstrated central deficiencies in BH4 and both controlled and open-label trials demonstrate a therapeutic effect of sapropterin in children with ASD (Frye et al., Some of the first cases of cerebral folate deficiency (CFD) were identified to have features of ASD (Ramaekers et al., 2005)