Phenylketonuria (PKU)

What is PKU?

PKU is a short form of a long word meaning “phenylalanine in the urine”. Phenylalanine, or “phe” for short, is a building block of protein. There are 20 different building blocks of protein. We eat protein in the form of meat, eggs, cheese, milk, beans and peanut butter. All food that contains protein also contains phe. If you eat protein, a hamburger for example, the food goes into your stomach and then into your blood stream for your body to break down and use to keep you healthy and strong.

The body breaks down the protein using things called enzymes. The best way to think of enzymes is as keys. They “unlock” doors to help your body do the jobs it needs to do to keep you healthy. People born with PKU are missing one enzyme. Their bodies cannot break down phe. It’s like a door is locked in their body and the key is missing. The phe then builds up in the blood and spills over into the urine. That is why it is called Phenylketonuria.

Picture a refrigerator door. If you went out and bought all your groceries and you came home and couldn’t get into the refrigerator, what’s going to happen? All the food is going to pile up outside the refrigerator. Soon it will fill up the whole kitchen and then spill out into the next room. In PKU, this is what happens. The key is missing to the refrigerator. Phe can’t get in through the door and builds up outside. Soon it has built up so much that it spills over.

Our bodies aren’t designed to cope with these high levels of phe. Having too much phe in the blood is like having too much alcohol to drink. Most of us can have 1 drink of alcohol and maybe feel a little tipsy but function OK. Drinking lots makes us feel sleepy, confused, emotional and not be able think clearly. High phe levels affect the person with PKU in much the same way. They are unable to think clearly, may be irritable and anxious and may cry easily.
Enter the name for this tabbed section: Treated PKU
How do people get PKU?
To have PKU, you have to be born with it. You cannot “catch” it or get it later in life. From the moment you are conceived, you have PKU. It is passed to the baby from the mother and father. The mother and father do not have to have PKU to pass it to their baby. They are called carriers of the gene that causes PKU.

Since 1965, all babies born in Canada are tested for PKU when they are born.
This way, treatment can be started right away.
How is PKU treated?
Since people with PKU are missing an enzyme (or key) to break down phenylalanine , they cannot eat high protein foods. These are foods to be avoided:
  • Meat: chicken, turkey, fish, beef, pork, lamb
  • Dairy: milk, cheese, yoghurt, cottage cheese, ice cream
  • Nuts and seeds including peanut butter
  • Tofu, beans and any other “meat substitutes” that vegetarians may eat to substitute protein in their diet
  • Food or drinks sweetened with Aspartame® such as Diet Coke®. Aspartame contains phenylalanine.
There are many other foods such as breads and pastas that contain protein. These foods are to be eaten in limited quantities only. Examples are french fries, crackers, regular pasta and bread.

Foods that can be eaten in unlimited quantities are free foods. These include fruits and vegetables and low protein products. Low protein products are special foods for people with PKU. They include cookies, pastas and breads made with special flour and contain very little phenylalanine.
Are people with PKU allergic to protein?
No, people with PKU are not allergic to protein. Remember that there are 20 building blocks of protein. We need to get all 20 to keep our bodies working right. People with PKU still need protein, but can only tolerate small amounts of one of protein’s building block--phenylalanine. So, people with PKU need 19 out of 20 building blocks of protein.

Where do they get their protein if they can’t eat it? They drink it! The special medical formula that people with PKU drink provides all the building blocks of protein except phe. It also gives them the vitamins and minerals they need. This special formula is a lot like the protein drinks that body builders use.
What happens if the person with PKU eats protein?
If the person with PKU eats too much protein, phe builds up in the blood. Remember the groceries and how the refrigerator was locked? Phe will build up in the blood like the groceries building up outside the refrigerator door.

High levels of phe not only make the person feel unwell, they can also damage the brain. Babies born with PKU and not treated with the special diet right from birth do not develop normally. They can be mentally challenged.
How long do people with PKU need to stay on the diet?
It is now known that the PKU diet is “for life”. Young people with PKU who have been on diet for the childhood and teen years are sometimes choosing to go off diet. Stopping the diet is harmful. The phe in the blood is still toxic to the brain even though the person has reached adulthood. Studies show that people off diet:
  • experience more cases of mental illness and psychological problems (e.g. being afraid to leave the house, schizophrenia, depression) than those on diet,
  • may develop problems with walking,
  • may experience tremors or seizures.
Other symptoms related to high phe levels include poor judgement, skin problems (eczema), headaches, lack of energy, mood swings, lack of ability to concentrate, loss of short term memory, poor performance in school or inability to hold a job, muscle weakness and poor personal relationships. High phe levels are not safe.
When is it too late to go on the PKU diet?
It is never too late to either start or return to the PKU diet. Although brain damage is not reversible, the “intoxication” effect of the high phe levels in the blood is reversible. By following the PKU diet, the person will feel better and reduce the symptoms related to high phe levels.
How can you tell if the phe levels are too high?
People with PKU test their blood every month by pricking their fingers and applying blood to a special blood dot card. The card is sent to the lab where the level of phe in their blood can be determined. A good phe level is 6 or less for life.
How can family and friends help?
Friends play a very special role in helping the person with PKU. It is very hard to constantly be faced with food temptations when you are trying to stick to a special diet. Understanding the challenges of living with PKU and offering a listening ear to frustrations will be really helpful.

Learn to prepare some favourite special dishes. If you are having a person with PKU over for a meal, ask them what they would like to eat and offer low-protein snack options such as:

• soda pop (not diet)
• fruit juices
• vegetable sticks with non-dairy dips
• fruit plate
• candies
Enter the name for this tabbed section: Late treated PKU
What is late-treated PKU?
Newborn screening for Phenylketonuria (PKU) of all babies born in British Columbia began in 1965. People with PKU who were born prior to the introduction of newborn screening may remain undiagnosed, and may have never tried the PKU diet.
People with PKU who were diagnosed late (several years after birth, or even in adulthood)) are called “late-treated”. These patients are usually cognitively impaired and often suffer effects from brain damage caused by high phe levels. Ideally treatment for PKU should begin at birth in order to prevent these effects.
Is there any benefit for someone with late treated PKU to follow a special PKU diet?
People with PKU born prior to the introduction of newborn screening may remain undiagnosed. However, such people, even if severely cognitively impaired, benefit from treatment. These benefits include improved seizure control, improvement in self-abusive behaviours, reduction in symptoms of chronic anxiety, improved socialization behaviours, fewer headaches and skin rashes. Treating these people may mean that less intensive supervision is needed, and their quality of life may be improved. They may also be able to reduce or eliminate the need to take medications for behaviour problems.

PKU results in progressive brain damage, even in adults. Therefore, treatment of people with PKU is now recommended for life, to prevent ongoing neurological injury.
If I know someone who is developmentally disabled and suspect they might have PKU, how can they be tested?
You can ask that the patient’s doctor order a blood test to check the plasma phenylalanine level (plasma amino acids). An elevated blood phenylalanine level would confirm the diagnosis of PKU. A level in the normal range rules out this diagnosis.

If the patient has PKU they can be referred to our clinic for treatment.
Enter the name for this tabbed section: Maternal PKU
Think you might be pregnant?
If you think you might be pregnant:
1. start the 200 mg phenylalanine diet immediately (see the diet under ‘useful resources’ at the bottom of this page)

2. do a pregnancy test

3. call the metabolic clinic immediately (604-875-5965 Monday to Friday 8 a.m. to 4 p.m. or after hours/holidays/weekends 604-875-4111 and ask for the endocrinologist on call)

4. be sure to drink all your formula

5. do a blood dot
What is Maternal PKU?
Women with Phenylketonuria (PKU) cannot process phenylalanine (PHE) properly in their body and this results in an elevated blood level of PHE. If a woman with PKU does not control her blood PHE levels during her pregnancy it can cause damage to her developing baby. This is called “maternal PKU” as it is the high PHE levels in the Mom that would cause damage to the baby.

When a woman becomes pregnant, she supports her baby by sharing nutrients from her diet, as well as oxygen through the placenta and the umbilical cord. Phenylalanine, like other amino acids, can cross the placenta to the baby. There is a 1.5:1 gradient of PHE across the placenta. This means that the baby is exposed to a higher concentration of PHE than what is in the pregnant woman’s blood. Because of this gradient, blood PHE levels that are safe for non-pregnant adults are harmful to the baby. The higher the blood PHE level in the Mom, the greater the damage there is to the developing baby.

Unfortunately, we know that phenylalanine is teratogenic (or harmful) to the developing baby. High levels of PHE in the Mom’s blood can result in birth defects (brain damage, small head, small baby, and heart defects), spontaneous abortions (miscarriages), poor growth and intellectual disability. This is why it is important for women with PKU to plan their pregnancies and establish control of phenylalanine levels before conceiving.
What PHE levels are too high in pregnancy?
Any woman who has blood PHE levels greater than 6 mg/dl—even if she does not carry the diagnosis of PKU—is at risk. Blood PHE levels should be between 2-6 mg/dL prior to conception and throughout pregnancy.
Can women with PKU have a healthy baby?
Yes! If the mother’s blood PHE levels are between 2-4 mg/dl before conception and during pregnancy, the risk to the baby approaches that of the general population. Even in the general population (e.g. people without PKU) the risk of having a baby with a birth defect is not zero. It is about 1%.
If I have PKU does that mean that my baby will too?
Usually the baby of a woman with PKU does not have PKU. It depends on if the father of the baby is a carrier of the PKU gene. The chance that a woman with PKU will have a baby with PKU is about 1%. Having an appointment with genetic counselor prior to conception will help couples to understand the risks that their baby will have PKU.
If a woman with PKU wants to have a baby what should she do?
All pregnancies should be carefully planned. Women with PKU who are considering pregnancy should make an appointment with the Adult Metabolic Diseases clinic as well as with their regular doctor (GP) before getting pregnant. It is recommended that women have their blood PHE levels in the target range of 2-4mg/dL for at least 3-6 months before trying for a baby.

In order to get blood PHE levels in the safe range, Mothers will need to drink a special drink (formula) in order to provide adequate PHE-free protein for the baby to grow. They will also need to carefully watch their dietary intake of phenylalanine by keeping daily food records and doing blood work twice a week (or more) to monitor their blood phe levels.

A couple considering a pregnancy should also meet with a genetic counselor to discuss the risks of maternal PKU and also the chance of the baby inheriting PKU.
Peer Resources
If you are interested in talking to someone who has PKU and has had a baby, please let us know.