Tetrahydrobiopterin (BH4) plays an important role in functional and metabolic cellular homeostasis, with additional effects on proliferation., 1, 2 immune responsiveness, 3, 4 and neuronal activity. 5–7 Mutations in either de novo biosynthetic or regeneration (salvage) pathways result in BH4 deficiency associated with diminished levels of seratonin and dopamine with progressive neurologic symptoms. 8, 9 The phenotypic presentation of these synthetic mutations can be predicted in large part by the role of BH4 as an obligatory cofactor in phenylalanine, tryptophan, and tyrosine hydroxylases (the rate-limiting enzymes for catecholamine and seratonin synthesis). The function of BH4 in these aromatic amino acid hydroxylases involves redox-active donation of electrons and reductive enzyme activation and is associated with a tightly coupled system for regeneration of BH4 from the oxidized dihydrobiopterin. 8, 10