Phenylketonuria (PKU) PKU Phenylalanine Hydroxylase Deficiency Phenylketonuria (PKU) is a genetic disorder characterized by the inability to metabolize phenylalanine, an amino acid, due to a deficiency in the enzyme phenylalanine hydroxylase (PAH). This leads to an accumulation of phenylalanine in the blood and brain, which can result in severe neurological and developmental issues.