About Phenylketonuria (PKU)

The basics:

PKU (Phenylketonuria) is a genetic metabolic disorder caused by a mutation in the gene that produces the enzyme phenylalanine hydroxylase (PAH). This enzyme is responsible for converting phenylalanine, an amino acid found in food, into another amino acid called tyrosine. In individuals with PKU, the PAH enzyme is either absent or significantly deficient, leading to an accumulation of phenylalanine in the bloodstream.

If left untreated, the excess phenylalanine can damage the brain and nervous system, causing developmental delays, intellectual disabilities, seizures, and other neurological problems. Phenylalanine is found in larger quantities in protein-rich foods such as meat, fish, eggs, dairy, and some nuts, so people with PKU must follow a strict, low-protein diet to limit its intake. They also consume specially formulated medical foods and medical formulas to ensure they get the necessary nutrients without the harmful buildup of phenylalanine.

PKU is typically diagnosed in infancy through newborn screening, which allows for early intervention. Early detection and strict dietary management, often starting in the first few weeks of life, are crucial for preventing brain damage and achieving normal development.

At one time it was believed that after brain development has occurred (usually in children between the ages of 6-10) those with PKU were taken off therapy with the assumption they would continue to be fine throught out the years. Later research showed that they can still be impaired, although less severely that if never treated. In the early 1980s, medical experts and organizations like the American Academy of Pediatrics began issuing more formal recommendations that PKU should be treated with lifelong dietary management. These guidelines emphasized maintaining strict control of phenylalanine levels throughout life to avoid the long-term cognitive and neuropsychological consequences associated with elevated levels. Advances in blood phenylalanine monitoring in the 1980s allowed for better control of blood levels and helped clinicians understand how fluctuations in phenylalanine could affect long-term outcomes. 

Many of those with PKU no longer need to rely solely on ensuring consumption of  a naturally lower protein foods, the use of Medical Foods and Medical Formulas.

In 2010 Health Canada approved the use of Biomarin's Kuvan (Sapropterin dihydrochloride) as a prescription medication for the treatment of phenylketonuria (PKU). Health Canada authorized its use, recognizing its efficacy in reducing blood phenylalanine (Phe) levels in patients with PKU>

In 2022 Health Canada approved the use of Biomarin's Palynziq (Pegvaliase)  to reduce blood phenylalanine concentrations in patients with phenylketonuria (PKU) aged 16 years and older who have inadequate blood phenylalanine control despite dietary management.

As the patent had expired on Biomarin's Kuvan, in 2023 Dr. Reddy's Labratories Health Canada approved their generic formulation, marketed under the name Reddy-Sapropterin, for use in pediatric patients aged 1 month to 16 years.

Other therapies including new pharmaceuticals, enzyme replacement therapy and gene therapy, are being explored and trialed to help manage PKU more effectively.

While PKU is a lifelong condition, many people with the disorder can live healthy, normal lives if they adhere to dietary restrictions and other medical recommendations. The importance of regular monitoring of phenylalanine levels in the blood is also critical for managing the condition over time.

Resources of Information:

Pastore, D., & Matalon, R. (1981). "Long-term outcomes of dietary therapy in phenylketonuria." Pediatric Clinics of North America, 28(3), 663-672. - This study explored the long-term effects of dietary therapy for PKU, discussing how higher levels of phenylalanine later in life can lead to developmental and cognitive impairments.

MacDonald, A., et al. (2000). "Cognitive function in early-treated phenylketonuria: Results of a 25-year follow-up study." Developmental Medicine & Child Neurology, 42(8), 591-598. - Although this study was published in 2000, it references earlier findings that lifelong control of blood phenylalanine levels is critical for optimal intellectual development, reinforcing the importance of continuous dietary management.

AAP. (1984). "The management of phenylketonuria." Pediatrics, 74(4), 789-797. - This guideline from the AAP highlighted the necessity of lifelong dietary management, with the recognition that elevated phenylalanine levels in adolescence and adulthood can have detrimental effects on cognitive function.

Rinaldo, P., et al. (2001). "Newborn screening for inherited metabolic disorders by tandem mass spectrometry." Journal of the American College of Nutrition, 20(5), 498-501. DOI: 10.1080/07315724.2001.10719022 - This paper discusses the adoption of tandem mass spectrometry for newborn screening programs, specifically focusing on how it has transformed the ability to screen for PKU and other metabolic conditions by detecting metabolites like phenylalanine with greater sensitivity.

For detailed information on Kuvan's approval and its use in Canada, you can refer to the Summary Basis of Decision provided by Health Canada 

For detailed information on Palynziq approval and use in Canada you can refer to the Summary Basis of Decision  provided by Health Canada.

For detailed information on Reddy-Sapropterin, you can refer to the Product Description information provided by Health Canada.