These may present with malignant phenylketonuria (PKU) and hyperphenylalaninemia (HPA)[5] and lead to a lack of certain neurotransmitters (dopamine, norepinephrine, epinephrine and serotonin).

To provide a basis for improving the understanding of the epidemiology, genotype/phenotype correlation and outcome of these diseases their impact on the quality of life of patients, and for evaluating diagnostic and therapeutic strategies a patient registry was established by the noncommercial International Working Group on Neurotransmitter Related Disorders (iNTD).

[8] The transcribed protein is the first and rate-limiting enzyme in tetrahydrobiopterin (THB, BH4) biosynthesis, catalyzing the conversion of GTP into 7,8-DHNP-3'-TP.

THB is an essential cofactor required by the aromatic amino acid hydroxylase (AAAH) and nitric oxide synthase (NOS) enzymes in the biosynthesis of the monoamine neurotransmitters serotonin (5-hydroxytryptamine (5-HT)), melatonin, dopamine, norepinephrine (noradrenaline), and epinephrine (adrenaline), and nitric oxide (NO), respectively.

Tetrahydrobiopterin (BH4) acts as a potent, diffusable antioxidant that resists oxidative stress and enables cancer cell survival.