For now, no curative therapy for PKU is available and restrictive diet, administration of the synthetic form of the PAH cofactor (acting as a pharmacological chaperone) or enzymatic substitution therapy with a pegylated form of the non-constitutive phenylalanine ammonia lyase (PEG-PAL), are the main options for PKU treatment, aiming to bring circulating L-Phe to levels lower than 360 μM in children, and 600 μM in adults, and closer to physiological values (≈120 μM) (Hafid and Christodoulou, 2015; Wegberg et al., 2017; Burton et al., 2020). This evidence concerns the gene PAH and phenylketonuria.