PKU is short for phenylketonuria (pronounced fen’-il-kee’-to-nu’-ria). PKU is a rare, inherited metabolic disease that results in developmental disability and other neurological problems when treatment is not started within the first two 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 and eating special low-protein food. The synthetic formula and special low-protein foods are expensive, but mostly covered here in Canada.
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 (before 10 days of age) and treatment is started right away, developmental disability 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 œmedical 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 & Management?
KUVAN – Tetrahydrobiopterin (BH4)
On April 30, 2010, Health Canada issued a Notice of Compliance to BioMarin Pharmaceutical Inc. for the drug product, Kuvan.
Kuvan is a pharmaceutical formulation of BH4, the co-factor for the enzyme phenylalanine hydroxylase (PAH). PAH hydroxylates Phe through an oxidative reaction to form tyrosine. In patients with PKU, PAH activity is absent or deficient. Treatment with BH4 can activate residual PAH enzyme, improve the oxidative metabolism of Phe, and decrease Phe levels in some patients. You need to talk to your clinician to see if Kuvan is right for you or your child. The only way to find out if you or your child is a responder to Kuvan is by trying Kuvan.
Some patients respond to Kuvan with a phe reduction, others experience a phe tolerance increase (with a reduction in the amount of medical foods needed) and some experience neuro-cognitive improvements. Everyone is different.
BioMarin Pharmaceutical (Canada) Inc. is committed to help Canadian Patients obtain access to Kuvan and sponsors a program, managed through a partner, Innomar Strategies Inc., to help ensure that all Canadians have access to this medication if they need it. Talk to your clinic if you are interesting in trying this PKU therapy.
PEG-PAL (PEGylated recombinant phenylalanine ammonia lyase or ‘PAL’) is an investigational enzyme substitution therapy for the treatment of phenylketonuria (PKU), an inherited metabolic disease caused by a deficiency of the enzyme phenylalanine hydroxylase (PAH).
PEG-PAL is being developed as a potential to treat patients whose blood Phe levels are not adequately controlled by Kuvan. Several centres in the US are participating in clinical trials but there are no sites in Canada. As of 2015, Biomarin owns the rights to PEG-PAL in Canada.
Preliminary work with gene therapies in animal models is experimental.
Home Phe Monitor
BioMarin has discontinued work on this project due to ongoing issues with accuracy at the low levels.
The much anticipated Home Phe Monitor (HPM) is being developed by BioMarin as a tool to help manage PKU. The HPM will allow patients to test their Blood-Phe level at any time of day, with just one drop of blood, and they will have the result within a few minutes! It is a very exciting development that many are eager to try.