Phenylketonuria (PKU)

What is phenylketonuria (PKU)?

Phenylketonuria (PKU) is a genetic condition that causes elevated levels of a substance called phenylalanine to build up in your body. Phenylalanine is found in the body as part of normal biochemical pathways, but problems arise when levels are persistently higher than normal.

Phenylalanine is an amino acid. Amino acids are molecules that form proteins. Many of the foods you eat that contain protein and the artificial sweetener aspartame have phenylalanine. If this condition isn't treated, buildup of phenylalanine in your body causes symptoms including challenges with cognitive development (intellectual disability).

What are the types of phenylketonuria (PKU)?

There are different types of phenylketonuria (PKU) based on the severity of the diagnosis. Symptoms are worse among severe cases in those who are untreated. Types of PKU include:

• Classic PKU (most severe).
• Moderate or mild PKU.
• Mild hyperphenylalaninemia (least severe).

Who does phenylketonuria (PKU) affect?

Phenylketonuria (PKU) can affect anyone who has mutations in both copies of the PAH gene. Studies suggest that there's a higher risk among people of Native American or European descent.

If a person with uncontrolled PKU has high levels of phenylalanine during pregnancy, this can cause intellectual disability, birth defects and other problems in their baby, even if the baby doesn't have PKU.

How common is phenylketonuria (PKU)?

In the United States, phenylketonuria (PKU) affects an estimated 1 in every 10,000 to 15,000 newborns each year.

What are the symptoms of phenylketonuria (PKU)?

Since diagnosis and treatment of phenylketonuria (PKU) most often occur shortly after birth due to an abnormal newborn screen, noticeable symptoms are very rare. Symptoms affect those with undiagnosed or untreated cases.

Symptoms of untreated PKU include:

• Eczema.
• Skin and/or hair discoloration (lighter compared to other members of their family).
• Small head size (microcephaly).
• A musty odor to their breath, skin or urine.

Severe symptoms of untreated PKU include:

• Behavioral problems.
• Developmental delays.
• Intellectual disabilities.
• Seizures (rare).

Children and adults with mild hyperphenylalaninemia are at a much lower risk for intellectual disabilities in the absence of treatment.

What causes phenylketonuria (PKU)?

Mutations in both copies of the PAH gene causes phenylketonuria (PKU). The PAH gene gives your body instructions to make an enzyme (phenylalanine hydroxylase) that's responsible for converting amino acids into components (proteins) that your body can use. When your body can’t process the amino acids that you eat in your diet, they build up in your blood and tissues. Your body is sensitive to phenylalanine. Too much phenylalanine in your body damages your brain.

Is phenylketonuria (PKU) dominant or recessive?

Phenylketonuria (PKU) is a genetic condition that passes to children from their parents in an autosomal recessive pattern. This means that babies receive one copy of the mutated gene that causes PKU from each parent during conception. In most cases, parents are carriers of the gene but don’t have symptoms of the condition.

How is phenylketonuria (PKU) diagnosed?

Healthcare providers confirm a diagnosis of phenylketonuria (PKU) shortly after birth as part of routine newborn screening via a blood test. If your baby’s phenylalanine levels in their blood sample are high, your provider will administer additional tests to confirm the diagnosis and the type of PKU, normally with additional blood or urine tests. Since PKU is a genetic condition, a genetic test can pinpoint the mutation responsible for symptoms.

Although the majority of PKU diagnoses occur shortly after a baby is born, providers can diagnose PKU at any age if newborn screenings weren’t completed.

Are there screening tests to diagnose phenylketonuria (PKU)?

A phenylalanine screening test identifies levels of phenylalanine in your blood. Newborns receive this test between 24 to 72 hours after birth as part of the newborn screen. Your healthcare 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.

How is phenylketonuria (PKU) treated?

Treatment for PKU is lifelong. It may include a special diet or medication.

Treatment could include:

• Eating a special diet low in phenylalanine but full of nutrients.
• Taking vitamins, minerals and supplements.
• Adding a supplemental medication called sapropterin dihydrochloride (Kuvan®) to break down phenylalanine in your body.

A medication called Pegvaliase (Palynziq®) allows people with PKU to eat an unrestricted diet without any supplements or Kuvan. This medication replaces the enzyme that helps to break down phenylalanine, which doesn’t work properly in PKU.

What foods contain phenylalanine?

A person diagnosed with phenylketonuria (PKU) needs to eat a special diet to limit the amount of foods that contain phenylalanine (if they're not treated with Pegvaliase). You can find phenylalanine in foods high in protein, including:

• Milk.
• Eggs.
• Cheese.
• Nuts.
• Fish.
• Chicken.
• Beef.
• Beans.
• Artificial sweetener (aspartame).

Is there a diet for phenylketonuria (PKU)?

A low-protein diet is best for people diagnosed with phenylketonuria (PKU) if they're not treated with Pegvaliase. You should avoid foods that are high in protein, such as meat, eggs and dairy products. If you or your child has PKU, talk with your healthcare provider or a dietitian about creating a diet that is well-balanced and full of essential nutrients.

What can I expect if I have phenylketonuria (PKU)?

Phenylketonuria (PKU) is a lifelong condition and most people living with it lead healthy lives. After diagnosis, regular blood tests to monitor the level of phenylalanine in your blood are necessary.

For those who are on a restrictive diet, many people benefit from working closely with a dietitian who can advise on the best foods to eat, what to avoid and how to get all the nutrients you need to stay healthy.

If you have PKU and are pregnant, your provider and/or dietitian will create a diet plan that ensures you receive proper nutrition while lowering your baby’s risk for complications.

How can I prevent phenylketonuria (PKU)?

There's no way to prevent phenylketonuria (PKU). If you plan on becoming pregnant and want to understand your risk of having a child with a genetic condition, talk to your healthcare provider about genetic testing.

How do I take care of myself?

Your phenylketonuria (PKU) diagnosis is lifelong, so stay up to date with your healthcare provider and get routine blood tests to monitor the level of phenylalanine in your body.

If you are on a restricted diet, you still need to eat foods and take vitamins to make up for the lack of protein in your diet. Make sure you follow your diet for your entire life to prevent symptoms that could be dangerous to your health.

If you plan on becoming pregnant, talk to your provider about genetic testing to understand your risk of having a child with a genetic condition.

When should I see my healthcare provider?

If you or your child develops symptoms of phenylketonuria, contact your healthcare provider for a thorough evaluation.

Before becoming pregnant or during your first prenatal examination, you can ask your doctor about testing (called carrier screening) to determine if you and your partner are at risk for having a child with PKU.

If you have PKU, visit your provider for regular blood tests to monitor your condition.

What questions should I ask my doctor?

• How do I make sure my baby gets enough nutrients to stay healthy?
• Do I need to take any vitamins or supplements?
• Is a low-protein diet enough to reduce my phenylalanine levels or do I need medication?