Usually, patients with HPA are detected through newborn screening for phenylketonuria (PKU) and defined as affected by milder to more severe forms (PKU/HPA) depending on serum phenylalanine levels,3 which is due to a remarkable allelic variability accounting for different related patterns of phenylalanine hydroxylase residual enzymatic activity (EC 1.14.16.1).4, 5, 6. This evidence concerns the gene PAH and phenylketonuria.