What is PKU?

Phenylketonuria (PKU), or phenylalanine hydroxylase (PAH) deficiency, is a lifelong, inborn error of metabolism that causes an amino acid, known as phenylalanine to build up in the blood. Phenylalanine, or “Phe,” is an amino acid found in many foods, especially those high in protein, such as chicken, meat, eggs, dairy, nuts, grains, and legumes. High or unstable blood Phe levels can cause a variety of signs and symptoms, including mental, behavioral, neurological, and physical problems.

Diagnosis of PKU

As a result of global newborn screening efforts implemented in the 1960s and early 1970s, virtually all people living with PKU who are under the age of 40 and living in developed countries have been diagnosed in the newborn period. PKU is characterized by elevated blood Phe levels. Those with the mild to moderate form of PKU have some residual active PAH enzyme and blood Phe levels ranging from approximately 600 µm/L to 1200 µm/L. Those with a more severe form of the disease have very little, if any, active PAH enzyme and blood Phe levels greater than 1200 µm/L.

Managing PKU

People with PKU need to keep Phe levels low. Treatment guidelines recommend keeping Phe levels between 120-360 µmol/L (2-6 mg/dL) for life. Treatment with a low-Phe diet should begin as early as possible and continue throughout life. Treatment with KUVAN, along with a low-Phe diet, should be considered for patients who respond to therapy.

The low-Phe diet

PKU is carefully managed with a low-Phe diet in order to control blood Phe levels. Phe is found in all protein-containing foods (eg, meat, eggs, dairy, nuts) as well as other foods that are not generally thought of as containing protein (eg, most wheat products and some vegetables and fruits). Phe-free formula and other supplements help people with PKU get necessary nutrients.


In combination with a low-Phe diet, KUVAN can offer an additional way to help lower blood Phe levels even more. Guidelines recommend that every person with PKU except those with two null mutations in trans try KUVAN to determine if it can help lower their blood Phe levels. KUVAN is available as both Tablets and Powder for Oral Solution.

Investigational Approaches for Treating PKU

Today, researchers are working to develop alternate treatment options for people living with PKU. The following are some of the approaches currently being evaluated for the treatment of PKU:

  • Enzyme Therapy:

    Enzyme therapy seeks to address the underlying enzyme deficiency associated with PKU by providing patients with enzyme capable of metabolizing Phe. Researchers are evaluating the use of various enzymes and routes of administration (e.g., oral and subcutaneous injection) for this purpose.
  • Gene Therapy:

    Gene therapy is being evaluated in preclinical studies as a means to allow in vivo (within a living body) production of the PAH enzyme. Like enzyme therapy, this approach is designed to address the underlying enzyme deficiency.
  • Non-Physiological Amino Acid (NPAA) Therapy:

    Non-physiological amino acids inhibit the shuttle systems that move large neutral amino acids (including phenylalanine) from the blood into the brain. Researchers are evaluating the ability of NPAAs to maximally restrict entry of Phe into the brains of PKU mice, while minimally altering the entry of other LNAAs.

Hepatocyte Transplantation:

To address the PAH deficiency in patients with PKU, this research involves replacing some of the defective liver cells with liver cells that have normal PAH activity. This technique involves removing part of the PKU liver and replenishing it with new cells (either from a donor or through stem cells). Hepatocyte transplantation has been used in other inborn errors of metabolism diseases with encouraging results and is currently being studies in PKU mice.

Additional Resources  

For additional information about PKU, please visit the following websites and others listed in the Patient/Physician Resource Library:


KUVAN® (sapropterin dihydrochloride) Tablets for Oral Use and Powder for Oral Solution are approved to reduce blood Phe levels in people with a certain type of Phenylketonuria (PKU). KUVAN is to be used with a Phe-restricted diet.

Important Safety Information

It is not possible to know if KUVAN will work for you without a trial of the medicine. Your doctor will check your blood Phe levels when you start taking KUVAN to see if the medicine is working.

Starting KUVAN does not eliminate the need for ongoing dietary management. Any change to your diet may impact your blood Phe level. Follow your doctor's instructions carefully. Your doctor and dietitian will continue to monitor your diet and blood Phe levels throughout your treatment with KUVAN to make sure your blood Phe levels are not too high or too low. If you have a fever, or if you are sick, your Phe level may go up. Tell your doctor and dietitian as soon as possible so they can make any necessary changes to your treatment.

Children younger than 7 years old treated with KUVAN doses of 20 mg/kg per day are at an increased risk for low levels of blood Phe compared with children 7 years and older. Frequent blood monitoring is recommended in this population to ensure that blood Phe levels do not fall too low.

Tell your doctor if you have ever had liver or kidney problems, have poor nutrition or have a loss of appetite, are pregnant or plan to become pregnant, or are breastfeeding or plan to breastfeed.

KUVAN is a prescription medicine and should not be taken by people who are allergic to any of its ingredients. KUVAN and other medicines may interact with each other. Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins, herbal and dietary supplements.

If you forget to take your dose of KUVAN, take it as soon as you remember that day. Do not take 2 doses in a day. If you take too much KUVAN, call your doctor for advice.

The most common side effects reported when using KUVAN are headache, runny nose and nasal congestion, sore throat, diarrhea, vomiting, and cough. Additional adverse reactions reported in connection with worldwide marketing include sore throat, heartburn or pain in the esophagus, inflammation of the lining of the stomach, indigestion, stomach pain, and nausea. These are not all the possible side effects seen with KUVAN. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

KUVAN can cause serious side effects, including:

  • Severe allergic reactions. Stop taking KUVAN and get medical help right away if you develop any of these symptoms of a severe allergic reaction:
    • Wheezing or trouble breathing
    • Nausea
    • Flushing
    • Lightheadedness or fainting
    • Coughing
    • Rash
  • Inflammation of the lining of the stomach (gastritis). Gastritis can happen with KUVAN and may be severe. Call your doctor right away if you have any:
    • Severe upper stomach-area discomfort or pain
    • Blood in your vomit or stool
    • Black, tarry stools
    • Nausea and vomiting
  • Too much or constant activity (hyperactivity) can happen with KUVAN. Tell your doctor if you have any signs of hyperactivity, including fidgeting, moving around or talking too much.

For more information, call BioMarin Patient and Physician Support (BPPS) at 1-866-906-6100. Please read the full Patient Information by clicking here.