While the majority of BH4 in the liver is maintained through the recycling pathway, consisting of quinoid dihydropteridine reductase (QDPR; also known as Dihydropteridine reductase; DHPR) and pterin-4α-carbinolamine dehydratase) (Werner et al., 2011; Himmelreich et al., 2021), a disruption of the de novo BH4 synthesis pathway will lead to BH4 deficiency and in most cases hyperphenylalaninemia (i.e., some GCH1 loss of function, all PTPS loss of function patients). Here, QDPR is linked to Hyperphenylalaninemia.