What Causes Phenylketonuria (PKU)?

What Causes Phenylketonuria?

Phenylketonuria, also known as PKU, is a rare inherited disorder that causes the amino acid phenylalanine to build up in the body. This buildup of phenylalanine, when left untreated, can cause a variety of symptoms, including cognitive developmental delays or intellectual disabilities. Individuals with PKU can treat this disorder by avoiding the consumption of foods containing protein and aspartame in order to limit the buildup of phenylalanine in the body and avoid the serious health effects that come with the buildup. The Special Olympics Arizona team is breaking down this rare disorder: what causes it, the risk factors, and treatments and cures that may be available.

What Causes PKU?

PKU is an inherited condition that is caused by a mutation in both copies of the PAH gene in the body. The PAH gene helps create phenylalanine hydroxylase, which is the enzyme that is responsible for the breakdown of phenylalanine in the body. Individuals without PKU will break down phenylalanine with this enzyme, and it will be turned into proteins or components that the body can use. Without the breakdown of phenylalanine, a dangerous buildup can occur, especially when individuals eat high protein foods. The body is very sensitive to phenylalanine, and a severe buildup can cause brain damage, among other cognitive and physical symptoms.

The genetic mutation that causes PKU can be mild, moderate, or severe. Individuals with a more mild case of PKU will have reduced production of the enzyme phenylalanine hydroxylase, resulting in lower levels of phenylalanine buildup. While this can still be dangerous, the symptoms are generally not as severe, especially when it comes to potential brain damage. However, any individual with any form of PKU must closely monitor their protein intake, with some individuals having a diet that cannot contain any protein or aspartame.

Phenylketonuria Risk Factors

There are no preventable risk factors that cause a child to be born with PKU; however, there are genetic factors to be aware of that increase the risk of a child being born with a mutated PAH gene, which may cause them to develop the disorder. The number one risk factor is having one or both parents who have PKU. If a child has two parents who have PKU, they will also develop the disorder. It is also a risk factor if they have both parents who are carriers of the mutated PAH gene, which can be determined through genetic testing.

Being of a certain racial or ethnic descent may increase the risk of a child being born with PKU. While PKU affects people of most racial and ethnic descents worldwide, within the United States, it is much more common for individuals of European descent to be born with the disorder. Individuals of African descent are much less likely to be born with the mutated PAH gene.

How Common Is Phenylketonuria?

PKU is rare, affecting an estimated 1 in every 10,000 to 15,000 births in the United States each year.

Is PKU Inherited?

PKU is a genetic condition that is inherited from the parents. This disorder or mutation is passed down in a recessive pattern, which means that for a child to be born with PKU, both parents must have had a mutated version of the PAH gene. Parents may be carriers of the PAH gene with no symptoms or signs of PKU. If only one parent is a carrier of the PAH gene, or if only one parent has PKU and the other parent is not a carrier of the PAH gene, the child will not develop PKU. Even if both parents are carriers of the PAH gene, it is not a guarantee that their child will develop PKU. This is because when both parents carry a recessive PAH gene, each one will pass a mutated PAH and a functioning PAH gene. It is possible for a child to inherit two non-mutated genes, or one mutated PAH gene and one non-mutated PAH gene; both combinations will result in a child not having PKU. If both parents carry a mutated PAH gene, there is a 25% chance each parent will pass on a normal PAH gene, in which case the child will not have the disorder. There is also a 25% chance that the child will receive two mutated PAH genes, causing the child to develop the disorder. There is a 50% chance the child will receive a normal PAH gene and a mutated PAH gene, making the child a carrier. In a case where both parents have the disorder, their child will also be born with PKU.

Can Phenylketonuria Be Prevented?

Phenylketonuria cannot be prevented; however, parents can gain a deeper understanding of their chances of having a child with a genetic mutation by speaking with their doctor about genetic testing. While genetic testing can provide background on the chances of having a child with a genetic mutation such as a mutated PAH gene, which can cause PKU, it will not provide any prevention methods, instead just providing more information on the likelihood of having a child with PKU.

Is There a Cure for Phenylketonuria?

There is currently no cure for PKU, but there are special diets and treatments that can help individuals with PKU live long and happy lives. Individuals with PKU will be put on a strict diet that greatly limits the amount of protein and aspartame they can consume. This special diet will be very low in phenylalanine, which could build up in the body and cause health issues, but high in other nutrients. There are also special vitamins, minerals, and supplements individuals can take to supplement any nutrients they cannot consume in their food. New developments in medicine have made it possible for individuals with PKU to loosen the restrictions on their diet or, in some cases, eat a regular diet with the proper use of medication. Medicines such as Kuvan, sapropterin dihydrochloride, and Palynziq, pegvaliase, have been developed to replace the enzyme that breaks down phenylalanine, allowing individuals to consume food regularly and rely on the medicine for the breakdown of protein and aspartame in the body.