Phenylketonuria (PKU) is a rare genetic condition that is present from birth (congenital). In PKU, the body is unable to break down a chemical called phenylalanine which then builds up in the blood and in the brain.

Left untreated, high phenylalanine levels disrupt the normal development of a child's brain and can cause severe learning difficulties and epilepsy. A person with the most severe learning difficulties has mental abilities similar to those you would expect to see in a one or two year old infant and would require 24 hour care for the whole of their life.


Phenylalanine is an amino acid. Amino acids are the 'building blocks' that the body uses to assemble proteins and other complex chemicals, such as some neurotransmitters ('messenger chemicals' that are used to transmit information around the brain).

The main source of phenylalanine for humans is food that is high in protein such us:

  • meat
  • fish
  • eggs
  • cheese
  • milk

Genetic mutation

PKU is caused by a genetic mutation. A genetic mutation is where some of the instructions that are found in all living cells become scrambled, causing certain cells to no longer work in the right way.

In most people the phenylalanine that is found in food is broken down by an enzyme known as phenylalanine hydroxylase (PAH). Proper breakdown of phenylalanine is needed for the body to make certain neurotransmitters.

In people with PKU, the PAH enzyme does not work properly due to the genetic mutation so it is less active. As a result, the phenylalanine levels in the blood and other tissues rise. Phenylalanine is thought to have a toxic (poisonous) effect on the brain and lead to deficiency in tyrosine(important for neurotransmission and brain development) resulting in brain damage and learning difficulties.

The treatment for PKU is both simple and effective.  It involves following a special, low-protein diet and taking regular dietary supplements which contain amino acids, vitamins and minerals. The aim is to keep the blood phenylalanine level within a specific target range.  The target range changes with age; the diet is very strict in early childhood but can be gradually relaxed as people get older.

How common is PKU?

PKU is a very rare condition. It is estimated that only 1 in every 4,500 babies born in Ireland will have PKU.

Both sexes are affected equally by PKU. The condition is slightly more common in white people, particularly those of Celtic descent (Scottish, Irish and Welsh). It is very rare in black people and those of Japanese descent.


All newborn babies who are born in Ireland, and those who are born in other developed countries, are routinely screened for high phenylalanine levels using the heel prick test which is carried out during the first week of a baby's life. The heel prick test involves taking a blood sample from the baby's heel to test for a number of rare, but serious, conditions, such as PKU.

If a high phenylalanine level is found on screening and confirmed by further testing, the baby will immediately be started on a low protein diet and a special supplement. Regular testing ensures that the phenylalanine level remains low. Keeping phenylalanine levels within the target range will prevent any damage to the brain and ensure that the child grows up with normal levels of intelligence.


With treatment, the outlook for PKU is excellent. As long as a person with the condition sticks to a  low protein diet throughout childhood their natural intelligence is generally unaffected.  Many adults find that the dietary restrictions can be challenging and annoying. 

Without treatment early in life, the outlook for PKU is very poor. Most people will develop severe learning disabilities and will require constant care.

People with phenylketonuria have to avoid eating any type of food that contains high levels of phenylalanine such as all types of meat 


Most babies with phenylketonuria (PKU) will appear healthy at birth.

Treated PKU

If dietary treatment is started within the first three weeks of life, people with PKU should not experience the severe learning difficulties that are associated with the condition.

Some children and adults with PKU do experience mild to moderate problems with certain high-level mental abilities and activities such as:

  • attention
  • planning
  • problem solving

However, these problems are usually related to the increased blood phenylalanine level and will improve with stricter treatment.

There is also evidence that adults with PKU may be more likely to develop certain mental health problems at some point in their life compared with the population at large. The most widely reported conditions in people with PKU are:

  • depression - feelings of extreme sadness that last for weeks or months
  • anxiety disorders -feelings of unease, such as worry or fear, that can be mild or severe
  • phobias,
  • particularly agoraphobia - which is an intense fear of certain situations, such as being in crowded places or leaving home
  • low self-esteem

Untreated PKU

A wide range of symptoms can occur if treatment for PKU is not started or delayed. The most common symptom of PKU is a learning disability. Usually, the longer treatment is delayed, the more severe the learning disability becomes.

Intelligence is measured using a type of test known as the intelligence quotient or IQ test. A person with average intelligence will score 100 in an IQ test (have an IQ of 100).

If a person with severe PKU is never treated, they will usually have an IQ score of less than 50 and require a lot of help with everyday activities. Even if PKU is not diagnosed on newborn screening, it is worth starting dietary treatment as it is sometimes possible to reverse some of the decline in intelligence. For example, in one case where a child's treatment was delayed until they were two years of age, they went from having a moderate learning disability to having average intelligence. 

Other symptoms of untreated PKU include:

  • behavioural difficulties, such as frequent temper tantrums and episodes of self-harm
  • very fair skin and hair 
  • eczema
  • epilepsy - a condition that affects the brain and causes a person to have repeated fits (seizures)


Genetic mutation

Phenylketonuria (PKU) is caused by a genetic mutation in a gene that is known as the human PAH gene. A gene is a single unit of genetic material. A genetic mutation occurs when the instructions that are carried in certain genes become 'scrambled'. This results in some of the body's processes not working in the normal way.

There are over 600 different types of mutation that can affect the PAH gene, all of which result in the same outcome. The body does not produce an enzyme that is needed to break down phenylalanine before reassembling it into more complex chemicals. This leads to the high levels of phenylalanine that are associated with PKU. Enzymes are proteins that speed up and control chemical reactions in the body.

Autosomal recessive mutation

All the genes in your body come in pairs. You receive one half of the pair from your mother and the other half from your father.

The mutation that causes PKU is an autosomal recessive mutation. This means that you need to receive two copies of the mutated gene in order to develop the condition - one from your mother and one from your father.

You will not develop PKU if you only receive one copy of the mutated gene from one of your parents, but you will carry the mutated gene.

If you are a carrier of the mutated gene and you conceive a baby with a partner who is also a carrier there is a:

  • 1 in 4 chance that the baby will receive a pair of normal genes
  • 1 in 2 chance that the baby will receive one normal gene and one mutated gene and become a carrier of the mutated PAH1 gene but will not develop any symptoms.
  • 1 in 4 chance that the baby will receive a pair of mutated genes and develop PKU


Newborn screening

All new born babies are routinely screened for phenylketonuria (PKU) by way of a blood test that is usually carried out about a week after a baby is born.

A sample of your baby's blood will be taken using a heel prick and sent to a laboratory where the levels of phenylalanine will be measured. If the levels are unusually high, a second blood sample will be taken to confirm the diagnosis. See Phenylketonuria - causes for more information about the genetics of PKU.

If the second test confirms high phenylalanine levels, you will be referred to a doctor who specialises in treating cases of PKU. You will also be referred to a dietician who is a healthcare professional with an interest in diet and nutrition at the National Centre for Inherited Metabolic Disorders. The dietician will be able to advise you about the changes that need to be made to your baby's diet. See Phenylketonuria - treatment | for more information.

Regular blood tests

After a diagnosis of PKU has been confirmed, your child will need to have regular blood tests to measure the levels of phenylalanine in their blood to assess how well they are responding to treatment.

It is recommended that children who are:

  • up to two years of age should have their blood tested once a week
  • two to six years of age should have their blood tested once every two weeks
  • over six years of age and all adults should have their blood tested once a month

Someone with PKU will usually need to continue having regular blood tests throughout their life.

It may be possible for you to receive training so that you can carry out your child's blood tests, or if you have PKU, so that you can test yourself. This will help to make testing more convenient.


Low protein diet

A low protein diet is the main type of treatment for phenylketonuria (PKU).  

Your dietician will be able to draw up a detailed dietary plan for your child and they will also be able to help revise the plan over time as your child gets older and their needs change.

It is beyond the scope of this article to provide a complete overview of all the recommendations and information regarding low protein diets.

In general terms a 'traffic light' approach to diet is recommended where foods are categorised as follows:

  • green foods - are those that are safe to eat because they contain very low levels of protein, although they should not be eaten to excess
  • amber foods - contain protein and must be carefully weighed; they will be eaten in different quantities according to your blood phenylalanine level
  • red foods - should never be eaten under any circumstances

Below are examples of green, amber and red foods.

Green foods

Examples of green foods include:

  • fresh fruit with the exception of bananas, figs and dates
  • most vegetables with the exception of asparagus, bean sprouts, broccoli, Brussels sprouts and cauliflower

There are also a number of specially designed low protein versions of popular products, such as flour, rice and pasta that are specifically designed for people with PKU and related conditions. Many of these special foods are available on prescription so you will not have to pay the full price for them.

Amber foods

Examples of amber foods include:

  • cornflakes
  • chips
  • baked beans
  • milk - a specially designed formula can be used as a milk substitute for babies and children
  • normal rice

Red foods

Examples of red foods include:

  • all types of meat
  • eggs
  • fish
  • cheese
  • beer -  lager and bitter
  • any food that has been baked using flour, such as bread

Dietary Supplements

As well as sticking to a low protein diet, people with PKU will also have to take regular dietary supplements. These contain all the essential nutrients that are absent from the low protein diet.  The supplements contain a mixture of all the amino acids (apart from phenylalanine) that are essential for the body to grow and remain healthy. Supplements are available in various different forms, including powders, drinks and tablets and need to be taken three or four times a day.


People with PKU also have to avoid food products that contain aspartame. Aspartame is an artificial sweetener that can be found in:

  • sugar substitutes, such as artificial sweeteners that are often used in tea and coffee
  • diet versions of fizzy drinks
  • chewing gum
  • squashes and cordials
  • some alcopops

All food products that contain aspartame or a related product should state on the packet 'contains a source of phenylalanine'.

There are also a number of medications that contain aspartame, such as some cold and flu remedies for children. It is a legal requirement for any medication that contains aspartame to state it on the patient information leaflet that comes with the medication.

You should always make sure you read the patient information leaflet carefully before giving any medication to your child.


Tetrahydrobioterin is a new type of medication that has proved to be effective at reducing the level of phenylalanine in some children and adults with mild PKU. Tetrahydrobioterin is a synthetic form of a vitamin which helps the PAH enzyme to work better.

Other therapies under investigation

- Enzyme substitution therapy:
        ~ Phenylalanine ammonia lyase
- Large neutral amino acid
- Gene therapy

Phenylketonuria and pregnancy

Women with PKU have to take particular care during pregnancy. This is because high levels of phenylalanine can damage the unborn baby leading to heart defects, learning difficulties and other problems. Fortunately, providing that the mother’s phenylalanine levels are strictly controlled during pregnancy, all of these problems can be avoided and there is no reason why any woman with PKU should not be able to have a normal, healthy baby.

Due to the need to keep phenylalanine levels very low throughout pregnancy, it is recommended that all women with PKU plan their pregnancies carefully. Ideally, they should be following a strict preconception diet and sending in blood monitoring once a week before they become pregnant.  Once the phenylalanine levels are within the target range for pregnancy, the couple can start to try to conceive.

During pregnancy, women are asked to send in blood samples twice weekly and will be in frequent contact with their dieticians. As soon as the baby is born, phenylalanine control can be relaxed and there is no reason why a mother with PKU cannot breast feed her baby.

If you do become pregnant when your phenylalanine levels are not adequately controlled it is important that you contact your PKU doctors and dieticians as soon as possible. Providing your phenylalanine levels can be brought under control within the first few weeks of your pregnancy, the risk of damage to the baby should be small. However, it will be necessary to monitor the pregnancy very carefully

Content provided by NHS Choices and adapted for Ireland by the Health A-Z.

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