Editing Phenylketonuria (section)

===Tetrahydrobiopterin-deficient hyperphenylalaninemia===
{{Main|Tetrahydrobiopterin deficiency}}

A rarer form of hyperphenylalaninemia is [[tetrahydrobiopterin deficiency]], which occurs when the PAH enzyme is normal, and a defect is found in the biosynthesis or recycling of the [[Cofactor (biochemistry)|cofactor]] [[tetrahydrobiopterin]] (BH<sub>4</sub>).<ref>{{Cite journal |vauthors=Surtees R, Blau N |year=2000 |title=The neurochemistry of phenylketonuria |journal=European Journal of Pediatrics |volume=169 |pages=S109–S113 |doi=10.1007/PL00014370 |pmid=11043156 |s2cid=26196359}}</ref> BH<sub>4</sub> is necessary for proper activity of the enzyme PAH, and this [[coenzyme]] can be supplemented as treatment. Those with this form of hyperphenylalaninemia may have a deficiency of tyrosine (which is created from phenylalanine by PAH), in which case treatment is supplementation of tyrosine to account for this deficiency.{{citation needed|date=September 2020}}

Levels of [[dopamine]] can be used to distinguish between these two types. [[Tetrahydrobiopterin]] is required to convert Phe to Tyr and is required to convert Tyr to [[L-DOPA]] via the enzyme [[tyrosine hydroxylase]]. L-DOPA, in turn, is converted to [[dopamine]]. Low levels of dopamine lead to high levels of [[prolactin]]. By contrast, in classical PKU (without dihydrobiopterin involvement), prolactin levels would be relatively normal.<ref>{{Cite journal |last1=Opladen |first1=Thomas |last2=López-Laso |first2=Eduardo |date=26 May 2020 |title=Consensus guideline for the diagnosis and treatment of tetrahydrobiopterin (BH4) deficiencies |journal=Orphanet Journal of Rare Diseases |volume=15 |issue=1 |page=126 |doi=10.1186/s13023-020-01379-8 |pmc=7251883 |pmid=32456656 |doi-access=free}}</ref>{{citation needed|date=September 2020}}

As of 2020, tetrahydrobiopterin deficiency was known to result from defects in five genes.<ref name="pmid32456656">{{Cite journal |vauthors=Opladen T, López-Laso E, Cortès-Saladelafont E, Pearson TS, Sivri HS, Yildiz Y, Assmann B, Kurian MA, Leuzzi V, Heales S, Pope S, Porta F, García-Cazorla A, Honzík T, Pons R, Regal L, Goez H, Artuch R, Hoffmann GF, Horvath G, Thöny B, Scholl-Bürgi S, Burlina A, Verbeek MM, Mastrangelo M, Friedman J, Wassenberg T, Jeltsch K, Kulhánek J, Kuseyri Hübschmann O |date=May 2020 |title=Consensus guideline for the diagnosis and treatment of tetrahydrobiopterin (BH4) deficiencies |journal=Orphanet Journal of Rare Diseases |volume=15 |issue=1 |pages=126 |doi=10.1186/s13023-020-01379-8 |pmc=7251883 |pmid=32456656 |doi-access=free}}</ref>