TH and Cognitive impairment: Insufficient or lack of BH4 will affect the activity of PAH and reduce the activity of tyrosine hydroxylase and tryptophan hydroxylase, thus affecting the synthesis of neurotransmitters (such as dopamine and serotonin) in the brain, which results in more severe symptoms of neurological damage and intellectual impairment in children (Leuzzi et al., 2010; Song et al., 2021).