Phenylketonuria (PKU)

Last Updated December 2020 | This article was created by familydoctor.org editorial staff and reviewed by Daron Gersch, MD, FAAFP

What is phenylketonuria (PKU)?

Phenylketonuria (PKU) is a rare genetic condition where babies are born unable to break down an amino acid called phenylalanine. This causes phenylalanine to build up. When phenylalanine levels get too high, it can damage the brain. This can lead to intellectual and developmental disabilities.

Phenylalanine is found in foods that contain protein. PKU is manageable, mostly through your diet. The key to living with PKU successfully is finding it early. That’s why all babies in the United States are screened for the disease at birth.

Symptoms of phenylketonuria

Newborns don’t initially have symptoms. But within a few months of birth, depending on the severity of the disease, symptoms begin to show. These include:

  • Smaller than normal head size (called microcephaly)
  • Hyperactivity
  • A musty or mouse-like odor in urine, breath, or skin
  • Lighter skin, hair, and eyes than their siblings
  • Jerking movements of the arms or legs
  • Tremors or seizures
  • Delayed development
  • Behavioral problems
  • Psychiatric disorders

If PKU isn’t controlled through changes in diet, it can cause severe and permanent intellectual and developmental disability.

What causes phenylketonuria?

PKU is an inherited disease. This means it’s passed down to the baby through the genes of the mother and father. It’s caused by mutations in the gene that helps make an enzyme called phenylalanine hydroxylase. This enzyme helps break down phenylalanine. When this gene doesn’t work right, the body can’t break down phenylalanine. It starts to build up and causes damage to nerve cells in the brain.

In the United States, you’re at higher risk of having PKU if you’re of European or Native American descent.

How is phenylketonuria diagnosed?

All newborn babies born in the United States are routinely tested for a range of diseases and conditions. One of the tests is a blood test that looks for the presence of phenylalanine hydroxylase. If that enzyme is missing, or if there is too much phenylalanine in the blood, more blood and urine tests will be done. These can confirm the diagnosis of PKU.

Nearly all cases of PKU are diagnosed through this newborn blood test.

Rarely, PKU could be missed during the screening process. For this reason, people of any age who have developmental delays or an intellectual disability are often tested for PKU.

PKU can also be diagnosed before the baby is born. A pregnant woman can request genetic testing be done to see if her unborn baby will have the disease. This is done through amniocentesis or chorionic villus sampling. This testing can be useful if the parents already have one child with PKU. Their chances of having another child with the condition are higher than average.

Can phenylketonuria be prevented or avoided?

Because PKU is a genetic condition, it can’t be prevented or avoided. Genetic testing is the only way to determine if people carry the defective gene. Some people may carry the gene but not have PKU. These people are called carriers. Both parents must carry one copy of the abnormal gene for the disease to be passed to the baby.

Phenylketonuria treatment

There is no cure for PKU. The most important treatment is a diet that limits foods with phenylalanine. This means the diet must be low in protein.

Newborns diagnosed with the disease must use special infant formula. This can be mixed with small amounts of breast milk or regular formula. It’s a delicate balance. Your baby does need some phenylalanine for normal development. But too much can hurt.

Children and adults who have PKU will also need to follow a low-phenylalanine diet. Phenylalanine is found in most protein foods. This includes all meats and fish, milk, cheese, eggs, nuts, soy, and beans. It’s also found in some non-protein foods. These include certain vegetables and fruit, certain breads, and beer. The sweetener aspartame, which releases phenylalanine when it’s digested, must also be avoided.

If you have PKU, you must follow a strict low-Phenylalanine diet both before becoming pregnant and during the pregnancy. Buildup of phenylalanine will damage your developing fetus, even if the baby hasn’t inherited the defective gene.

The U.S. Food and Drug Administration has approved the medicine sapropterin dihydrochloride (brand name: Kuvan) for the treatment of PKU. Kuvan can help the body break down phenylalanine. However, the medicine only helps some people. Even for those it does help, it doesn’t decrease enough phenylalanine. Those taking the medicine must still follow a low-phenylalanine diet.

Living with phenylketonuria

Because the PKU diet is so limiting, it’s hard to get all the essential nutrients the body needs. A special daily formula can help ensure those with PKU get proper nutrition. Taking supplements may also be necessary. For example, fish oil can replace some of the fatty acids (the basic building blocks of lipids, or fats) missing from the standard PKU diet. Those fatty acids can help improve neurological development.

Each person with PKU has a different level of phenylalanine they can tolerate. If you have PKU, you must work closely with your doctor to develop your individual diet. You need to eat enough phenylalanine for healthy growth and development. However, you can’t eat so much that it will be harmful to your health. Going to the doctor often, and getting regular blood tests, helps keep everything in check.

The PKU diet is very restrictive. But it must be followed. Babies who start the diet soon after birth usually develop normally. Many show no symptoms of PKU. Those people who stay on the diet throughout their lives have better overall physical and mental health than those with PKU who don’t. Support from friends and family or a PKU support group can be helpful when facing the challenges that come with this diet.

Questions for your doctor

  • Should I get genetic testing for PKU?
  • If I have PKU, what should I do during my pregnancy to protect my baby?
  • What determines the severity of PKU?
  • What should I feed my child?
  • What happens if my child eats a food he’s not supposed to eat?
  • How long will my child need to follow the restricted PKU diet?
  • How often do I need to bring my baby with PKU in for testing?
  • Will my next child have PKU?
  • What can and can’t I eat as part of the PKU diet?