The History of PKU

Early research milestones

Since the discovery of PKU as a new disease in 1934, scientific interest in the disease has advanced at an astonishing pace, taking PKU from obscurity to the forefront of cutting-edge biotechnology research—from an unidentified syndrome with devastating and permanent consequences to a condition whose management promises to help people live productive and fulfilling lives. At this pace, it is hard to imagine what discoveries lie ahead in the first years of the 21st century.

1934: PKU is discovered²³

In 1934, a Norwegian doctor named Asbjorn Folling described a group of mentally retarded patients who had a strange odor. We learned that this smell was caused by phenylacetic acid and that the patients' urine had large amounts of a phenylketone called phenylpyruvic acid. Hence, the condition was given the name phenylketon-uria. Not only was Folling the first to understand the disease and its relationship with phenylalanine, he was also the first to suggest its genetic nature and advise a form of management through dietary restriction.

1951: PKU management combines dietary restriction and protein replacement²⁴

Less than 20 years after its discovery, PKU was well known in the scientific community as a disease of protein digestion that could be controlled by a special diet. However, it wasn’t until Horst Bickel, a German professor, developed a protein supplement that people with PKU had any hope of living a somewhat normal life. Bickel’s first protein drink was unflavored.

1966: A simple diagnostic test becomes the international standard for newborn screening

In 1958, the Guthrie test, named after its discoverer, Robert Guthrie of Minnesota, was the first affordable test for screening hyper Phe in newborns. It gained recognition rapidly due to its simplicity, which made its widespread implementation cost-effective. In 1966, newborn screening with the test became the standard in hospitals in the United States.

The test, still widely used today, requires only a drop of blood, compared with about 4 teaspoons of blood in previous tests.

This simple test made it possible to catch virtually every PKU case in infancy, assuring that the disease could be properly managed from the outset and that mental retardation due to PKU could be avoided. The pioneering efforts of Guthrie played a pivotal role in helping diagnose the majority of people living with PKU today.

2007: The first drug therapy for PKU is introduced

KUVAN™ (sapropterin dihydrochloride) Tablets, the first prescription drug therapy approved for the treatment of PKU, became available to patients in 2007. Produced by BioMarin Pharmaceutical Inc, KUVAN is indicated to reduce blood Phe levels in patients with hyperphenylalaninemia (HPA) due to BH4-responsive PKU and is to be used in conjunction with a Phe-restricted diet.

Learn more about KUVAN.

KUVAN™ (sapropterin dihydrochloride) Tablets 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 for KUVAN

High blood Phe levels are toxic to the brain and can lead to lower intelligence and a 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 and change your diet 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 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 the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.