Phenylketonuria (PKU) is the result of a defective gene that is passed on from each parent to the child. This is known as an autosomal recessive trait. Parents sometimes have PKU themselves, but more often they are carriers of the gene. This means they have the defective gene, but do not have PKU itself. Parents who are considering having a child can have genetic testing to see if they are carriers for PKU. When both parents carry the defective gene, they have a one in four chance that each child will have PKU.

Children who inherit this genetic deficiency from each parent are missing or are deficient in an enzyme called phenylalanine hydroxylase. This enzyme processes the amino acid phenylalanine in the body. If only one parent passes on the defective gene, the child will not have PKU.

This absence or deficiency of phenylalanine hydroxylase causes levels of phenylalanine and two other phenylalanine derivatives to build up in the body. High levels of these substances in tissues and the bloodstream are toxic to the central nervous system, which can result in brain damage and other neurological symptoms.