General Condition Information
- Phenylketonuria (Classic)
- Phenylketonuria (phenylalanine hydroxylase)
- Hundreds of babies are born with this condition every year in the United States.
- It is more common in babies of Irish or Turkish descent.
- It is less common in African, Ashkenazi Jewish, and Japanese babies.
- Visit GeneReviews to learn more about how often this condition occurs.
What is Classic phenylketonuria
Classic phenylketonuria (PKU) is an inherited (genetic) condition that prevents the body from processing proteins correctly. Your body breaks down the protein that you eat into parts called amino acids. Your body then uses those amino acids to make other proteins that it needs to function.
PKU is a form of hyperphenylalaninemia. Hyperphenylalaninemia results in high levels of an amino acid called phenylalanine in the body.
Babies with PKU are unable to make an enzyme called phenylalanine hydroxylase (PAH) correctly. This enzyme helps change phenylalanine into another amino acid called tyrosine.
PKU can be more or less severe depending on how well PAH can break down phenylalanine. When the body does not make PAH correctly, but it can still process some phenylalanine, this results in a condition called non-PKU hyperphenylalaninemia. When PAH is missing or damaged, phenylalanine is not broken down and starts to build up in the body. This more severe condition is known as PKU.
High levels of phenylalanine can damage the body, including the brain. If untreated, this damage leads to the signs and symptoms of the condition. However, with early diagnosis and treatment, children with PKU can have near-normal health and development.
Newborn Screening and Follow-Up
Newborn screening for PKU is done using a small amount of blood collected from your baby’s heel. To learn more about this process, visit the Blood Spot Screening page.
During screening, a special machine measures how much phenylalanine is in your baby’s blood. Babies with high levels of phenylalanine and low levels of tyrosine might have PKU.
If your baby’s blood spot screening result for PKU is out-of-range, your baby’s health care provider will contact you. Together, you will discuss next steps and follow-up plans.
An out-of-range screening result does not mean that your baby definitely has the condition. It does mean that your baby needs more follow-up testing. To learn more about screening results, visit the Blood Spot Screening Results page.
Your baby may need the following tests after an out-of-range screening result:
- Blood and/or urine tests
- Genetic testing using a blood sample
You should complete any recommended follow-up testing as soon as possible. Babies with this condition can have serious health problems if they are not diagnosed and treated quickly.
False-positive newborn screening results for this condition are rare. However, some situations can affect screening results:
- Babies who are receiving supplemental nutrition (also known as total parenteral nutrition or TPN)
- Babies whose mothers have PKU
Newborn screening helps babies lead healthier lives. If your baby has an out-of-range result, follow up with your health care provider quickly. It is important to follow their instructions. Your baby may need to get treatment right away, even if they are not showing signs or symptoms. In some cases, your baby’s health care provider may decide it is best to watch (monitor) your baby to decide next steps. Careful monitoring and early treatment will help your baby stay as healthy as possible.
Signs of PKU can vary widely and may appear anytime from a few months of age to early childhood. These signs occur when phenylalanine reaches harmful levels in the body. This happens when foods or formulas containing protein continue to be eaten.
Signs of the condition may include the following:
- Behavior problems/irritability
- Dry, scaly skin (eczema)
- Musty body odor
- Lighter hair and skin than family members
- Intellectual disability
The condition is caused by a change in the PAH gene. This gene gives your body instructions for making the enzyme phenylalanine hydroxylase (PAH). This enzyme helps break down the amino acid phenylalanine.
Without a working PAH gene, your baby’s body cannot make this enzyme, or it makes PAH enzymes that don’t work well.
If phenylalanine is not broken down, it can build up to harmful levels. Nerve cells in the brain are very sensitive to phenylalanine levels, so high levels of phenylalanine can cause brain damage.
- PKU is an autosomal recessive condition. Babies inherit it when each parent passes down a nonworking PAH gene to their baby. Only babies with two nonworking PAH genes—one from the mom and one from the dad—have this condition.
- People with one working copy and one nonworking copy of the PAH gene are called carriers.
- Carriers do not have or develop the condition. However, they may pass down a nonworking copy of the gene to their children.
- If two parents are carriers of a nonworking copy of the PAH gene, they have a 1 in 4 chance of having a child with PKU.
- Carriers for PKU often do not know they are carriers before having a child with the condition. In most cases, families have no history of the condition until the birth of a child with PKU.
- Parents who already have a child with PKU still have a 1 in 4 chance of having another child with PKU. This 1 in 4 chance stays the same for future children.
- Genetic counselors and medical geneticists can help families learn about this condition and the chance of having children with it. Visit the National Society of Genetic Counselors to find a genetic counselor and the American College of Medical Genetics and Genomics to find a medical geneticist.
- Mothers who have PKU need to receive treatment and follow their special diet during pregnancy. High amounts of phenylalanine in the blood of a pregnant woman can affect the baby she is carrying, even if the baby does not have PKU. Babies who are exposed to high phenylalanine levels while they are in the womb might have intellectual disabilities and other health problems (heart defects or small head size).
Treatment and Management
It is important to talk to your health care provider about which treatment(s) are best for your baby. The goal of treatment is to prevent the health problems caused by this condition.
Treatments may include the following:
- Restricted diet low in foods that contain phenylalanine
- Special phenylalanine-free formula
- Medications that contain a substance called BH4 that helps the body process phenylalanine
Children who receive early and ongoing treatment for PKU can have healthy growth and development.