Does hyperphenylalaninemia always indicate a deficiency in the enzyme phenylalanine hydroxylase?
=> No, it does not. There may be other defects present, such as those involved in regeneration of the cofactor tetrahydrobiopterin (BH4), that would cause elevated levels of phenylalanine. In cases where the defect is not in the enzyme PAH, but involves production or regeneration of BH4 , there may be aberrant levels of neopterin and biopterin. The elevation or depression of the urinary pterins can in fact be used to deduce the exact defect in the metabolism of BH4. Neurotransmitter levels might also be affected, since the synthesis of certain neurotransmitters depends on the oxidation of tyrosine and tryptophan in reactions that use the cofactor BH4.
