Put simply, PKU means that a person's body is unable to break down the amino acid phenylalanine which is found in all protein containing foods. As a result of the body's inability to clear this amino acid, a build-up occurs. Persistent elevation of phenylalanine or its by-products is toxic to the brain and in patients with classical PKU it leads to profound intellectual handicap, often with seizures and aggressive behaviour.
The only way of treating this disorder is by adhering to a strict diet that restricts protein to the minimum requirements necessary for normal growth. The diet is supplemented with specifically designed medical foods. Intellectual handicap caused by this disorder can be prevented provided the diet is implemented within the first weeks of life.
The diet however is difficult, costly and inconvenient. People with classical PKU cannot eat any meat, fish or dairy products. They may have to accurately weigh the fruit and vegetables that they eat. They have to buy special low protein products such as rice, pasta and bread. Sticking to the diet is not always easy and therefore a treatment that is simple to administer and well tolerated could revolutionise the management of all patients with PKU diet.
It has become apparent over the last few years that high doses of tetrahydrobiopterin (BH4) in some PKU patients may help to reduce the blood phenylalanine concentration. This in turn could mean that at least some of the individuals with PKU may be able to have a more "relaxed" diet or even come off the diet altogether. The BH4 comes as a tablet and is taken orally; just a few tablets a day. In fact, a pilot study at the Children's Hospital at Westmead using BH4 showed that up to half of individuals studies showed a positive response, as judged by a drop of phenylalanine levels by at least 30%. This is potentially a great step forward in the management of individuals with PKU, representing the first significant advance in the treatment of PKU in over 40 years. However, the BH4 tablet is expensive and not currently available through the Pharmaceutical Benefits Scheme. It is hoped that this will become available at some stage.
Certain mistakes in the PKU gene are known to be associated with being responsive to BH4. The Children's Hospital at Westmead PKU research team is about to embark on the next phase of their studies, using genetic analysis to allow them to be able to identify PKU sufferers who are likely to respond favourably to BH4. This important research has been made possible by sponsorship by the PKU (Phenylketonuria) Association of NSW Inc. and most recently by the most generous support of the Italian Chamber of Commerce & Industry. It is anticipated that when BH4 finally becomes available we will be well poised to be able to identify those individuals with PKU who would benefit the most.
Prepared by Professor John Christodoulou and Professor Bridget Wilcken
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