Phenylketonuria - PKU

PKU is short for phenylketonuria (pronounced fen'-il-kee'-to-nu'-ria)

PKU is a rare, inherited metabolic disease that results in mental retardation and other neurological problems when treatment is not started within the first few weeks of life.

How can PKU affect a person?

People with PKU are missing an enzyme to break down protein in food, specifically one aminio acid. This amino acid is called phenylalanine, often called PHE (pronounced ‘fee’.)
Since this amino acid cannot be completely processed, it builds up in the blood and excess amounts cross the blood-brain barrier. When excess amounts build up, brain damage and other neurological problems result.

Most children and adults with PKU must follow a special diet. The PKU diet involves strictly controlling the intake of natural protein (which contains phenylalanine), drinking a synthetic phenylalanine-free protein formula (known as medical food) and eating special low-protein food. The synthetic formula and special low-protein foods are expensive.

How often are children with PKU born?

PKU is inherited as an autosomal recessive trait. In other words, two people who conceive a child must both be carriers of the gene in order for there to be a chance that their infant will have PKU. When two carriers conceive a child, there is a one in four or 25% chance for each pregnancy that the baby will have PKU.

It is estimated that PKU occurs with a frequency of one in 12,000 newborns in North America. This amounts for about 300 new cases each year.
The incidence varies in other parts of the world, it occurs with a frequency of 1 in 4,500 new born babies in Ireland and Turkey, 1 in 10,000 in most of Europe, and 1 in 11,000 in South America.

Is it possible to prevent the symptoms?

YES, fortunately, if the child is diagnosed early (between 7 and 10 days after birth) and treatment is started right away mental retardation can be prevented. There is a screening program for PKU available for Canadian children, which takes place shortly after birth (newborn screening). All children with PKU have access to treatment. To maintain proper health and development the blood PHE level must be kept in good control throughout the child's life.

How is PKU treated?

• Reduce phenylalanine intake through low PHE diet
• Provide necessary alternative to natural protein through “medical formula”
• Periodic monitoring of blood PHE levels

How is the PKU Diet?

The diet for the most severe form of PKU eliminates all of the very high protein foods since all protein contains phenylalanine. This means that all concentrated sources of protein must be eliminated from the diet in order to limit the amount of phenylalanine. The diet does not allow consumption of meat, fish, poultry, milk, eggs, cheese, ice cream, legumes, nuts, or many products containing regular flour.

A synthetic formula is used as a nutritional substitute for the eliminated foods. This formula is very expensive.
The diet is supplemented with special low protein foods and weighed or measured amounts of fruits, vegetables and some grain products. These foods are allowed in quantities that suit the individual child's tolerance for phenylalanine.

How is PKU diagnosed?

Every baby born in Canada is supposed to be tested for signs of elevated phenylalanine. This effects about one baby in 12,000 in Canada. The reason for this universal newborn screening for PKU is that a baby with PKU does not show signs or symptoms until after irreversible harm has occurred. The lack of early signs and symptoms means the best mother and father working with the best doctors and nurses do not have a good chance of preventing permanent brain damage. That why we call newborn screening a modern miracle.

Most Canadian babies have been screened for PKU since the 1960s. We do not screen children born in other countries when their families move to Canada.

What’s New in PKU Treatment?

A new drug for PKU has been approved in the USA called Kuvan™ and a small number of Canadians have been able to obtain this therapy by their doctor’s application to Health Canada’s Special Access Program. This drug is a synthetic version of a natural co-factor required for the PKU enzyme. We know it works for some but not all people with PKU.

Another drug (enzyme replacement) called PEG-PAL™ started in May, 2008 the first phase of clinical trials at six centers in the USA. No centres in Canada are participating in this first trial.

Initial trials with chemical blockers to stop excess phenylalanine from entering the brain have taken place in the USA and Europe.

Preliminary work with gene therapies in animal models is experimental.