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Phenylketonuria (PKU)

Phenylketonuria (PKU) is a lifelong genetic disorder in which an enzyme that does not work properly prevents the body from metabolizing (or process) one of the normal building blocks of protein. The building block is an essential amino acid, phenylalanine (Phe), which is found in most foods including meat, bread, eggs, dairy, nuts, and some fruits and vegetables. When PKU is not treated, Phe levels rise in the blood and can become toxic to the brain. High Phe levels in the brain cause problems including IQ loss, memory loss, difficulty concentrating, mood disorders and severe intellectual disabilities. Fortunately, all newborn infants are tested for PKU so untreated PKU is rarely seen. PKU affects about 13,000 people in the U.S. and 50,000 people worldwide.

What Are the Symptoms of Phenylketonuria?

As mentioned above, through newborn screening for PKU, infants are diagnosed within a few weeks of birth and symptoms can be prevented with immediate and lifelong treatment. Prior to newborn screening, untreated PKU would cause the following symptoms: intellectual disability, brain damage, epilepsy (seizures), musty body odor, and decreased skin and/or hair pigmentation. While obvious symptoms of untreated PKU are rarely seen today, long term effects of elevated Phe in the brain can lead to neurocognitive and neuropsychological concerns in patients. Neurocognitive concerns mean that patients may have problems with executive function skills. Examples of executive function skills include memory recall, processing speed (the ability to easily do simple or previously-learned tasks) and the ability to focus.  Neuropsychological concerns include a higher risk of anxiety and depression in patients with PKU.

What Causes Phenylketonuria?

PKU is a genetic disorder caused by changes (mutations) in the PAH gene that contains the instructions for the cells in our bodies to make an enzyme called phenylalanine hydroxylase (PAH). PAH converts the amino acid Phe which is in many things that we eat and drink to another amino acid, tyrosine. Tyrosine (Tyr) is important for healthy brain function. In patients with PKU, the PAH does not work properly.

Many of the foods we eat contain protein. Proteins are made of building blocks called amino acids and phenylalanine (Phe) is one of them. In PKU, the enzyme that would normally convert Phe to the amino acid tyrosine (Tyr) does not work properly. 

When Phe is not converted to Tyr, its levels rise in the blood and brain. High levels of Phe are toxic to the brain. This can lead to things like memory loss, anxiety, depression and problems concentrating.

How Is Phenylketonuria Diagnosed?

All newborn infants have a blood sample obtained from a heel stick at about 24 hours after birth for testing of at least 35 different disorders. If the screening test is positive for PKU, additional blood and urine tests are done to confirm the diagnosis.

How Is Phenylketonuria Treated?

Phenyketonuria is treated with a special diet and formula. Infants, children and adults with PKU are placed on a diet that limits the amount of protein (and therefore Phe) that they eat and drink. In addition, patients with PKU must also drink a special medical formula. It contains the essential amino acids and nutrients that are needed to grow and stay healthy, minus the Phe.    

Two medicines are available to treat PKU (Kuvan®) sapropterin and pegvaliase (Palynziq™). The goal of these medicines is to allow patients with PKU to safely increase the amount of protein in their diet. Sapropterin, is taken by mouth. It may be used to treat children and adults with PKU. It works to lower Phe levels in the blood by boosting the body’s own ability to break down Phe. However, not all people with PKU respond to this treatment. Patients who do respond to sapropterin may be able to eat more protein as part of their diet.    

In 2018, a new medicine called pegvaliase was FDA-approved to treat adults with PKU. It is given by daily subcutaneous injection (a shot under the skin). Pegvaliase contains an enzyme that works as a substitute for the PAH enzyme that is not working properly in patients with PKU. Response to pegvaliase varies, and it can take several months for blood Phe levels to decrease. In time, patients treated with pegvaliase may also be able to eat more protein as part of their diet.    

All forms of PKU treatment require regular blood testing to check blood Phe levels. This is very important to ensure that the treatment is keeping the Phe level in the right range for each patient. It also allows treatment adjustments to be made as needed.     

At Lurie Children’s, PKU is treated by a team of health care providers that includes a doctor or nurse practitioner, registered nurses (RNs), dietitians, a social worker and genetic counselor. The team sees more than 250 patients with PKU each year. We provide comprehensive care from the first clinic visit through the transition to adult care.

We also participate in clinical research in areas that include natural history studies, patient registries and additional treatment options for patients with PKU. Please see our Research page for more information.

Additional Information & Resources 

National PKU Alliance

PKU Organization of Illinois

National Organization for Rare Disorders (NORD)