Phenylketonuria

Phenylketonuria (PKU) is a type of amino acid metabolism disorder.

 

Phenylketonuria (PKU) is a type of amino acid metabolism disorder. It is inherited. If you have it, your body can't process part of a protein called phenylalanine (Phe). Phe is in almost all foods. If your Phe level gets too high, it can damage your brain and cause severe intellectual disability. All babies born in U.S. hospitals must now have a screening test for PKU. This makes it easier to diagnose and treat the problem early.

The best treatment for PKU is a diet of low-protein foods. There are special formulas for newborns. For older children and adults, the diet includes many fruits and vegetables. It also includes some low-protein breads, pastas and cereals. Nutritional formulas provide the vitamins and minerals you can't get from their food.

Babies who get on this special diet soon after they are born develop normally. Many have no symptoms of PKU. It is important to stay on the diet for the rest of your life.

Children with untreated PKU appear normal at birth. But by age 3 to 6 months, they begin to lose interest in their surroundings. By age 1 year, children are developmentally delayed and their skin has less pigmentation than someone without the condition. If people with PKU do not restrict the phenylalanine in their diet, they develop severe intellectual and developmental disabilities.

Other symptoms include:

  • Behavioral or social problems
  • Seizures, shaking, or jerking movements in the arms and legs
  • Stunted or slow growth
  • Skin rashes, like eczema 
  • Small head size, called microcephaly
  • A musty odor in urine, breath, or skin that is a result of the extra phenylalanine in the body
  • Fair skin and blue eyes, due to the body's failure to transform phenylalanine into melanin, the pigment responsible for a person's coloring

Nearly all cases of PKU are diagnosed through a blood test done on newborns.1

Newborn Screening for PKU

All 50 U.S. states and territories require that newborns get screened for PKU. In addition to the United States, many other countries routinely screen infants for PKU.

How are newborns tested for PKU?

Health care providers conduct a PKU screening test using a few drops of blood from a newborn's heel. The blood sample, which can be used to screen for other conditions as well, is tested in a laboratory to determine if it has too much phenylalanine in it. The newborn screening test should be performed by the child's pediatrician if the mother did not give birth in a hospital or is discharged from the hospital before the test is performed.

What if my newborn tests positive for PKU?

If your newborn's screening test comes back positive for PKU, your child will need additional tests to confirm that he or she definitely has the disorder. It is very important to follow your health care providers' instructions for further tests. These tests may be blood or urine tests that may show whether or not the child has PKU. If your child does have PKU, getting treatment quickly will help protect your child's health.

Your health care providers may also suggest genetic testing to look at the mutations in genes that cause PKU. This testing is not required to figure out whether your child has PKU, but it will help identify the specific type of genetic mutation causing the disorder. This information may be useful for determining the best treatment plan going forward.

Screening for PKU Later in Life

In the United States, newborn screening identifies nearly all people born with PKU. However, there are concerns that cases of PKU could be missed due to errors at any step of the screening process—specimen collection, laboratory procedures, treatment initiation, or clinical follow-up. Missed cases are considered to be extremely rare. Because of these rare cases, health professionals recommend PKU testing if a person of any age has developmental delays or an intellectual disability.

Testing during Pregnancy

A pregnant woman can request a prenatal DNA test to learn whether or not her child will be born with PKU. To perform this test, a health care provider takes some cells, either through a needle inserted into the abdomen or a small tube inserted into the vagina. A genetic counselor who understands the risks and benefits of genetic testing can help explain the choices available for testing.This discussion may be particularly useful for parents who already have one child with PKU, because they have a higher-than-average chance of conceiving another child with the disorder.

 

There is no cure for PKU, but treatment can prevent intellectual disabilities and other health problems.  A person with PKU should receive treatment at a medical center that specializes in the disorder.

The PKU Diet

People with PKU need to follow a diet that limits foods with phenylalanine. The diet should be followed carefully and be started as soon after birth as possible. It is recommend that people with PKU stay on the diet throughout their lives for better physical and mental health.

It is especially important for a pregnant woman with PKU to strictly follow the low-phenylalanine diet throughout her pregnancy to ensure the healthy development of her infant.

 People with PKU need to avoid various high-protein foods, including:

  • Milk and cheese
  • Eggs
  • Nuts
  • Soybeans
  • Beans
  • Chicken, beef, or pork
  • Fish
  • Peas
  • Beer

People with PKU also need to avoid the sweetener aspartame, which is in some foods, drinks, medications, and vitamins. Aspartame releases phenylalanine when it is digested, so it raises the level of phenylalanine in a person's blood.

 Often, people with PKU also have to limit their intake of lower-protein foods, such as certain fruits and vegetables. However, a PKU diet can include low-protein noodles and other special products.

The amount of phenylalanine that is safe to consume differs for each person. Therefore, a person with PKU needs to work with a health care professional to develop an individualized diet. The goal is to eat only the amount of phenylalanine necessary for healthy growth and body processes but not any extra. Frequent blood tests and doctor visits are necessary to help determine how well the diet is working. Some relaxation of the diet may be possible as a child gets older, but the recommendation today is lifelong adherence to the diet.  Following the diet is especially important during pregnancy.

A PKU Formula

People who follow the PKU diet will not get enough essential nutrients from food. Therefore, they must drink a special formula.

A newborn who is diagnosed with PKU should receive special infant formula. The formula may be mixed with a small amount of breast milk or regular infant formula to make sure the child gets enough phenylalanine for normal development but not enough to cause harm.

Older children and adults receive a different formula to meet their nutritional needs. This formula should be consumed every day throughout a person's life.

In addition to the formula, health care professionals may recommend other supplements. For example, fish oil may be recommended to help with fine motor coordination and other aspects of development.

Medication for PKU

The U.S. Food and Drug Administration (FDA) has approved the drug sapropterin dihydrochloride (Kuvan®) for the treatment of PKU. Kuvan® is a form of BH4, which is a substance in the body that helps break down phenylalanine. However, having too little BH4 is only one reason a person may not break down phenylalanine. Therefore, Kuvan® only helps some people reduce the phenylalanine in their blood. Even if the medication helps, it will not decrease the phenylalanine to the desired amount and must be used together with the PKU diet.

When the FDA approved Kuvan®, the agency suggested that research on the medication continue to determine its long-term safety and effectiveness.

Other Treatments for PKU

NICHD-supported researchers and other scientists are exploring additional treatments for PKU. These treatments include large neutral amino acid supplementation, which may help prevent phenylalanine from entering the brain, and enzyme replacement therapy, which uses a substance similar to the enzyme that usually breaks down phenylalanine. Researchers are also investigating the possibility of using gene therapy, which involves injecting new genes to break down phenylalanine. That would result in the breakdown of phenylalanine and decreased blood phenylalanine levels.