Diarrhea and vomiting are also relatively common, seen in at least 1% of people. Interactions
No interaction studies have been conducted. Because of its mechanism, tetrahydrobiopterin might interact with dihydrofolate reductase inhibitors like methotrexate and trimethoprim, and NO-enhancing drugs like nitroglycerin, molsidomine, minoxidil, and PDE5 inhibitors. Combination of tetrahydrobiopterin with levodopa can lead to increased excitability. Functions
Tetrahydrobiopterin has multiple roles in human biochemistry. The major one is to convert amino acids such as phenylalanine, tyrosine, and tryptophan to precursors of dopamine and serotonin, major monoamine neurotransmitters. It works as a cofactor, being required for an enzymes activity as a catalyst, mainly hydroxylases. Cofactor for tryptophan hydroxylases
Tetrahydrobiopterin is a cofactor for tryptophan hydroxylase (TPH) for the conversion of L-tryptophan (TRP) to 5-hydroxytryptophan (5-HTP). Cofactor for phenylalanine hydroxylase
Phenylalanine hydroxylase (PAH) catalyses the conversion of L-phenylalanine (PHE) to L-tyrosine (TYR). Therefore, a deficiency in tetrahydrobiopterin can cause a toxic buildup of L-phenylalanine, which manifests as the severe neurological issues seen in phenylketonuria. Cofactor for tyrosine hydroxylase
Tyrosine hydroxylase (TH) catalyses the conversion of L-tyrosine to L-DOPA (DOPA), which is the precursor for dopamine. Dopamine is a vital neurotransmitter, and is the precursor of norepinephrine and epinephrine. Thus, a deficiency of BH4 can lead to systemic deficiencies of dopamine, norepinephrine, and epinephrine. In fact, one of the primary conditions that can result from GTPCH-related BH4 deficiency is dopamine-responsive dystonia; currently, this condition is typically treated with carbidopa/levodopa, which directly restores dopamine levels within the brain.
The hormonal and intellectual deficits created by these therapies causes significant impairment of the survivors.In current clinical studies, the patients are divided into low-, standard- and high-risk groups:

Depending on the study, healing rates of up to 100% are achieved in the low-risk group (usually WNT-activated). The current efforts are therefore moving in the direction of reducing the intensity of the therapy and thus the negative long-term consequences while confirming the high healing rates. In the HIT-SIOP PNET 4 study, in which 340 children and adolescents of the standard-risk group between the ages of four and 21 from several European countries participated, the 5-year survival rate was between 85% and 87% depending on the randomization. Around 78% of the patients remained without relapse for 5 years and are therefore considered to be cured. After a relapse, the prognosis was very poor. Despite intensive treatment, only four of 66 patients were still alive 5 years after a relapse. A US study involved 161 patients between the ages of three and 21 with a high-risk profile. Depending on the randomization, half of the patients additionally received carboplatin daily during the radiation. The 5-year survival rate of patients with carboplatin was 82%, those without 68%. The European SIOP PNET 5 study is currently taking place and will run until April 2024, in which an attempt is made to confirm the promising results with carboplatin during irradiation in the standard risk group. Epidemiology
Medulloblastomas affect just under two people per million per year, and affect children 10 times more than adults.