Phenylalanine is an amino acid obtained normally through the diet, but can be harmful if excess levels build up, causing intellectual disability and other serious health problems.

[1] This condition is inherited in an autosomal recessive pattern, which means two copies of a specific gene in each cell are altered in order for the individual to be afflicted.

Additionally, mutations of the MTHFR gene (A1298C variant) and DHFR can interfere with the recycling of BH4 and lead to less severe, but still clinifically significant, deficiencies of BH4.

[citation needed] BH4 is a compound that helps convert several amino acids, including phenylalanine, to other essential molecules in the body.

It is also involved in the production of serotonin, dopamine, epinephrine, and norepinephrine – neurotransmitters that transmit signals between nerve cells in the brain.

[citation needed] Other underlying causes of tetrahydrobiopterin deficiency are:[2] Directed by screening newborn for elevated plasma levels of phenylalanine.

[8] Subclinical deficiency can be found in individuals with poor diet (including low intake of folate or vitamin C) or genetic mutations in the MTHFR genes, which are involved in BH4 synthesis and recycling.