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What is PKU?

PKU (Phenylketonuria) is an inherited metabolic disorder caused by a deficiency of the enzyme, phenylalanine hydroxylase (PAH). This enzyme is required for the breakdown of phenylalanine (Phe), an amino acid found in most protein-containing foods. Without sufficient amounts or activity of PAH, Phe accumulates to abnormally high levels in the blood. In the United States, PKU occurs in 1 in 10,000 to 1 in 15,000 newborn babies, according to the National Human Genome Research Institute.
Clinical manifestations of sustained high Phe levels include a variety of serious neurological complications, including:

  • Mental retardation and brain damage
  • Mental illness
  • Seizures and tremors
  • Cognitive problems
  • Executive function challenges

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 typical blood Phe levels ranging from approximately 600 µm/L to 1200 µm/L prior to treatment. 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 prior to treatment.

Managing PKU

People living with PKU strive to manage their disease and maintain normal, non-toxic blood Phe levels by adhering to a highly Phe-restricted diet. This diet consists of natural foods that are low in phenylalanine, modified low protein foods, and specially formulated medical foods. For the reasons below, this diet is very difficult to adhere to, especially through adolescence and adulthood:

    1. Most natural foods contain phenylalanine. Milk and dairy products, meat, fish, chicken, eggs, beans and nuts contain very high Phe levels and must be excluded from the diet. Fruits, vegetables, and breads and pastas also contain Phe, but since the Phe levels in these foods are low, measured amounts can be included in the diet.

    2. Medical food diets that are low in Phe and provide necessary nutrients (e.g., tyrosine) are expensive and can be unpalatable.

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.
  • LNAA Therapy:
    Phe is one of several large neutral amino acids (LNAA) that cross the blood-brain barrier via a specific type of carrier. To prevent elevated levels of Phe from entering the brain and causing neurological damage, researchers are evaluating the use of supplemental levels of other naturally occurring LNAA. It is hypothesized that large quantities of LNAAs ‘compete’ for the same carrier that transports Phe across the blood-brain barrier thereby blocking Phe from entering the brain.

Kuvan® (sapropterin dihydrochloride), a therapy based on the enzyme cofactor 6R-BH4, is the first and only FDA-approved treatment for PKU. The remainder of these approaches are in the investigational stage of product development–some in nonclinical global studies (involving animal models) and some in clinical studies (involving humans)–and have not received marketing authorization from regulatory agencies.

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 (100 mg) and Powder for Oral Solution (100 mg and 500 mg) is approved to reduce blood Phe levels in patients with hyperphenylalaninemia (HPA) due to tetrahydrobiopterin- (BH4-) responsive Phenylketonuria (PKU). Kuvan is to be used with a Phe-restricted diet.

Important Safety Information

High blood Phe levels are toxic to the brain and can lead to lower intelligence and decrease in the ability to focus, remember, and organize information. Any change you make 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.
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 see if they have to adjust your treatment to help keep your blood Phe levels in the desired range.

Kuvan is a prescription medicine and should not be taken by people who are allergic to any of its ingredients. Tell your doctor if you have ever had liver or kidney problems, are nursing or pregnant or may become pregnant, have poor nutrition or are anorexic. Your doctor will decide if Kuvan is right for you. Tell your doctor about all the medicines you take.

The most common side effects reported when using Kuvan are headache, diarrhea, abdominal pain, upper respiratory tract infection (like a cold), throat pain, vomiting, and nausea.

To report SUSPECTED ADVERSE REACTIONS, contact BioMarin Pharmaceutical Inc. at 1-866-906-6100, or FDA at 1-800-FDA-1088 or

Kuvan is available by prescription only. To learn more, please visit for full prescribing information. If you have any questions about this information, please talk with your doctor.

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