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Phenylketonuria (PKU)

Phenylketonuria (PKU) is a rare genetic disease that babies are born with. It occurs due to the lack of an enzyme that helps their bodies break down a specific amino acid. Without this enzyme, the amino acid builds up in your baby’s blood and brain. It can cause toxic effects without treatment. Treatment includes a special diet and medication.

What Is Phenylketonuria (PKU)?

Phenylketonuria (PKU) is a rare genetic disease. It causes a building block of protein (an amino acid) called phenylalanine to build up in your baby’s body. Babies born with phenylketonuria (pronounced “FEH-nil-KEE-tone-yoor-ee-uh”) can’t break down phenylalanine. So, high levels of the amino acid start to collect in their bloodstream.

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Too much phenylalanine is toxic to your baby’s brain. Without treatment, it can cause brain damage. This can lead to serious complications like developmental delays and intellectual disability.

Fortunately, all babies born in U.S. hospitals are screened for PKU disease shortly after birth. If your baby’s provider diagnoses PKU, they can begin treatment right away. So, your baby will likely avoid severe symptoms and develop typically.

Symptoms and Causes

Physical symptoms of PKU can range from nausea to tremors
Along with developmental delays and intellectual disability, PKU can cause various physical symptoms.

What are the symptoms of phenylketonuria?

Babies with phenylketonuria appear healthy at birth. Without treatment, symptoms of PKU will develop slowly over a period of three to six months. During this time, you may notice the first signs of the condition, like developmental delays.

By 1 year old, your baby may have other phenylketonuria (PKU) symptoms, including:

  • A musty odor to their breath, sweat or pee (urine)
  • Changes to their skin, hair and eyes (lighter color compared to other members of their family)
  • Eczema
  • Growth delay
  • Nausea and vomiting
  • Tremors

Along with developmental delays and intellectual disability, severe PKU symptoms may eventually develop. These include:

  • Behavioral problems, like frequent temper tantrums and self-harm
  • Hyperactivity
  • Learning disabilities
  • Seizures

Pregnancy and PKU

If you have untreated phenylketonuria and you’re pregnant, you’re at a high risk for miscarriage. Babies born to mothers with unmanaged PKU disease may have:

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If your PKU is well managed, you can have healthy babies.

Phenylketonuria causes

Changes (pathogenic variants) in the PAH gene cause phenylketonuria. The PAH gene gives your body instructions on how to make an enzyme called phenylalanine hydroxylase (PAH). This enzyme is responsible for processing the amino acid phenylalanine.

When there are changes in the PAH gene, the PAH enzyme may be missing or defective. Without the PAH enzyme, your baby can’t break down phenylalanine. It builds up in their body, leading to the symptoms of the disease.

What is phenylalanine?

Phenylalanine is an essential amino acid. An essential amino acid is one that your body needs but doesn’t produce naturally. You must get it from the foods you eat. Phenylalanine can be found in many high-protein foods, like meat, eggs and dairy.

Normally, your body uses the phenylalanine it needs and then converts the excess into other substances it uses. But when your baby lacks PAH, phenylalanine builds up in their blood and brain.

How is phenylketonuria inherited?

Phenylketonuria is inherited in an autosomal recessive pattern. That means a baby needs to receive both copies of the changed gene (one from each biological parent) to develop the condition.

Diagnosis and Tests

How doctors diagnose PKU

Your baby’s healthcare provider will diagnose phenylketonuria shortly after birth. Newborns in every hospital in the U.S. (and many other countries) are tested for PKU disease as part of routine newborn screening. Your baby’s provider will take a sample of blood from your baby’s heel by poking it with a small needle. Only a few drops of blood are necessary for this test.

Newborn screening looks for high levels of phenylalanine in your baby’s blood. If your baby’s phenylalanine levels are high, their provider will order additional blood tests or urine tests. They may also request a genetic test in order to pinpoint the change in the PAH gene responsible for their condition.

Almost all cases of PKU are diagnosed between 24 and 72 hours after birth. But healthcare providers can diagnose the condition at any age. It’s very rare, but providers can miss some cases during the screening process. You can also get tested if you didn’t receive a newborn screening.

Prenatal testing

If you’re pregnant, a prenatal genetic test can tell you if your baby’s at risk for genetic conditions, including phenylketonuria. A genetic counselor can help you decide if testing is right for you. Then, they can explain the results of the test.

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Prenatal genetic testing may be useful if you already have a child with PKU. This is because you have a higher risk of conceiving another baby with the condition.

Management and Treatment

How is PKU treated?

There’s no cure for PKU. But treatment for the condition can prevent symptoms and severe complications from developing. Phenylketonuria treatment is lifelong. It consists of a special diet (eating plan) and possibly medication. If you stop following the eating plan or taking the medication, symptoms will quickly return.

Phenylalanine diet

People with PKU must carefully follow a special eating plan low in phenylalanine. Foods high in protein — like meat, eggs and dairy — contain phenylalanine. But your body still needs some protein to function. A dietitian can create an eating plan specialized for you that’s well-balanced and full of nutrients. The goal is to consume just enough phenylalanine to keep your body running and no more.

You also need to avoid the artificial sweetener aspartame. This is because aspartame releases phenylalanine into your bloodstream when your body digests it. Aspartame is in many foods, drinks and medications — especially those labeled “diet” or “sugar-free.” Examples of products containing aspartame include:

  • Certain cereals
  • Reduced-sugar yogurt
  • Diet soda
  • Flavored sparkling water
  • Sugar-free gum
  • Low-calorie sweeteners
  • Chewable vitamins
  • Cough drops

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If you have phenylketonuria and you’re pregnant, it’s especially important to follow this eating plan throughout your pregnancy. This will ensure your baby is born healthy. Newborns with PKU need to start on a special phenylalanine-free formula right away.

PKU medications

The U.S. Food and Drug Administration (FDA) approves two medications for the possible treatment of phenylketonuria:

  • Sapropterin dihydrochloride (Kuvan®): Kuvan may benefit some people with PKU. This medicine helps break down phenylalanine in your body. It’s a tablet that you take by mouth. You must also continue to strictly follow the phenylketonuria diet.
  • Pegvaliase (Palynziq®): For some adults with unmanaged blood levels of phenylalanine, Palynziq may help. This medicine replaces the enzyme that helps break down phenylalanine. You inject this medication under your skin. There’s potential that Palynziq will allow adults to eat more protein or even have a normal diet. But you must continue to work with your provider to determine if you need to make any changes to what you eat.

Outlook / Prognosis

Can people with PKU live a normal life?

Phenylketonuria (PKU) is a lifelong condition with no cure. But with early diagnosis, you can manage PKU and minimize its impact on your health.

You or your child will likely need to be on a low-protein eating plan for life to protect your health. This can be daunting and exhausting to plan your life around. But you’re not alone. Your dietitian will be a go-to source of expertise. You might also want to join a support group of other people living with PKU to learn from their experiences.

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If PKU is causing distress, reach out to a mental health professional for help. Your mental health is just as important as your physical health.

Additional Common Questions

What are phenylketonurics?

Just as people with diabetes sometimes prefer to be called “diabetics,” the same holds true for people with PKU. They may prefer the term “phenylketonuric.”

Many different foods, drinks and medications are made with the artificial sweetener aspartame. Aspartame contains phenylalanine. Companies that make products with aspartame are required to add a warning label to their packaging. So, on products like diet soda or sugar-free gum, you’ll see the warning: “Phenylketonurics: Contains phenylalanine.” This is to help phenylketonurics avoid them.

A note from Cleveland Clinic

When you or your newborn receives a phenylketonuria (PKU) diagnosis, it may be hard to accept. The thought of having to restrict certain foods for the rest of your life may be overwhelming. Work closely with a dietitian to create an eating plan that’s phenylalanine-free but still delicious and nutritious. PKU is a lifelong condition. But by carefully following your eating plan and checking your phenylalanine levels frequently, you can manage how it affects your life.

Care at Cleveland Clinic

Do certain health conditions seem to run in your family? Are you ready to find out if you’re at risk? Cleveland Clinic’s genetics team can help.

Medically Reviewed

Last reviewed on 07/16/2025.

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