Experimental models of eNOS activity indicate that the BH4:BH2 ratio, which we found to be significantly decreased in CM compared to all other groups, is the measurement that most strongly correlates with NOS uncoupling [37].The hyperphenylalaninemia that we previously described in UM and CM [18] was one of the initial observations that led us to test the hypothesis of impaired BH4 in CM, since BH4 is an essential cofactor for the enzymatic hydroxylation of phenylalanine to tyrosine. This evidence concerns the gene NOS2 and Hyperphenylalaninemia.