PKU is caused by mutations in the gene that helps make an enzyme called phenylalanine hydroxylase (pronounced fen-l-AL-uh-neen hahy-DROK-suh-leys), or PAH. This enzyme is needed to convert the amino acid phenylalanine into other substances the body needs. When this gene, known as the PAH gene, is defective, the body cannot break down phenylalanine.
Amino acids help build protein, but phenylalanine can cause harm when it builds up in a person's body. In particular, nerve cells in the brain are sensitive to phenylalanine.
Many different PAH mutations result in problems with breaking down phenylalanine. Some mutations cause PKU, others cause non-PKU hyperphenylalaninemia (pronounced HAHY-per-fen-l-al-uh-nih-NEE-mee-uh) and others are silent mutations that do not have an effect.1
PKU is inherited from a person's parents. The disorder is passed down in a recessive pattern, which means that for a child to develop PKU, both parents have to contribute a mutated version of the PAH gene. If both parents have PKU, their child will have PKU as well.
Sometimes, a parent does not have PKU but is a carrier, which means the parent carries a mutated PAH gene. If only one parent carries the mutated gene, the child will not develop PKU.
Even if both parents carry the mutated PAH gene, their child still may not develop PKU. This is because a child's parents each carry two versions of the PAH gene, only one of which they will pass on during conception.
If both of a child's parents are carriers, there is a 25% chance that each parent will pass on the normal PAH gene. In this case, the child will not have the disorder. Conversely, there also is a 25% chance that the carrier parents will both pass along the mutated gene, causing the child to have PKU. However, there is a 50% chance that a child will inherit one normal gene from one parent and one abnormal one from the other, making the child a carrier.
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