PKU fact file

Phenylketonuria (PKU) is a rare inherited condition that causes a build-up of Phenylalanine. Phenylalanine (phe) is one of 20 amino acids that make up the building blocks of protein. When we take in protein from our diet our bodies break it down into amino acids to repair damaged tissues or for growth.

 
People with PKU lack a sufficient amount of the enzyme called phenylalanine hydrolase (PAH) that helps to convert Phenylalanine into the necessary amino acid, Tyrosine. This lack of conversion results both in an accumulation of Phenylalanine and a lack of Tyrosine. The extent to which PAH is effective at breaking down phenylalanine into Tyrosine is determined by the genetic mutation that tells the body how to produce PAH. Persistently high levels of Phenylalanine and low levels of Tyrosine in babies and children result in poor brain growth and development, causing irreversible and severe learning difficulties. This genetic mutation causes variation in the extent to which individuals with PKU are affected.

 
PKU is a lifelong condition that has a significant impact on day-to-day life. It used to be advocated that once a young person had stopped growing and developing they should return to a normal diet. However, this is no longer considered to be the case and a diet for life is advised.
 
Throughout their lifetime, someone with PKU has to become an expert in knowing how to manage their condition and how this condition affects them. Not all people with PKU experience symptoms when they have high phenylalanine levels. These symptoms can be very non-specific, such as generally feeling fatigued or having low energy levels, and could be the result of a variety of other causes.

 

Phenylketonuria (PKU) can be diagnosed by a blood test showing the levels of all amino acids; a PKU affected person has significantly raised Phenylalanine levels. It is also now possible to identify the genetic fault (PAH lies chromosome 12 but there are more than 400 disease causing mutations known).


PKU affects around 1:10,000 babies born in the UK every year and males and females are affected equally. With an estimated population in the UK of 62.3 million in mid-2010, it could be extrapolated that there are approximately 6200 people living in the UK affected by PKU.

All babies born in the UK are screened routinely for PKU and 4 other conditions (sickle cell, cystic fibrosis, congenital hypothyroidism & MCADD - medium chain acyl CoA dehydrogenase deficiency). Screening for PKU has meant that these children no longer develop severe learning difficulties and poor brain growth and development, as this is prevented by a specialist diet of restrictions and supplements.


Being a young adult with this condition presents particular challenges. They may be faced with the urge to go out socially with friends, but feel they want to avoid situations where they need to eat out or drink alcohol. Young adults with PKU may not want their peers to know they are different and may choose to limit their social interactions.


Due to the teratogenic (causing significant harm to a foetus) nature of phenylalanine, any pregnancy has to be carefully planned during pregnancy the mother's phenylalanine levels need to be significantly lowered though a stricter diet and closer monitoring.


Much of the focus on living with PKU is about planning; removing some of the spontaneity that young people in particular tend to value. The long-term effects of living with PKU are still not known, as screening and treatment is relatively recent - about 40 years ago.

Management of adults with PKU has changed significantly during this time. Undiagnosed, affected adults with severe learning difficulties and very challenging behaviour have been diagnosed retrospectively and started on a low protein diet and supplements, with significantly positive results.


These results and the recent research in adults with PKU on their mood and sustained attention have now resulted in a recommendation of a diet for life. High phenylalanine levels in adults with PKU have been found to have a direct effect, decreasing mood and reducing the ability to concentrate. New management options are being developed to try and increase the amount of natural protein that can be taken in a diet and improve their quality of life, but the challenges of the restricted life choices and being a long-term patient remain.

There is no cure for Phenylketonuria (PKU); it is managed through dietary restriction and use of phenylalanine free amino acid supplements. With this management the potential neurological damage is avoided and children grow up to be normal independent adults. It is classified as an inborn error of metabolism.

 
PKU was first diagnosed in the 1930's when it was discovered that babies who failed to make PAH developed what was then called ‘mental retardation' which could be prevented by restricting their protein intake. A severely restricted low-protein diet can also be damaging, as babies and children need enough of the other amino acids to grow and develop normally. Therefore in the 1950's supplements were developed providing the first effective management of the condition. These supplements contained all of the other amino acids essential for growth and development.

 
Put simply, treatment is in two forms - restrictions and supplements. 
 
While a low protein diet and the use of supplement drinks is the main stay of treatment for PKU, this is a lot harder than it appears. Protein is present in animal proteins, such as meat and fish, but it is also present in high levels in large numbers of other foods too including bread, cheese, some alcoholic drinks and pasta.

 
The reality is that someone with PKU needs to ensure they know how much phenylalanine they consume each day in protein-containing foods. They do this by weighing the food stuffs they eat and, over many years, learning what they can safely eat.

 
To make this simpler, food is calculated in "exchanges", or how much of each food is equivalent to 50mg of Phenylalanine. For example, 1 ounce of cow's milk (30 ml) or about 4 large chips (45 mg) are equivalent to one exchange. Children or pregnant women may be limited to only 3 exchanges a day. It means that it is extremely important to plan any aspect of life that may involve food or diet, eating out or using convenience foods can be very challenging.
 
To increase the range of foods that a person with PKU can consume, low protein products have been developed such as pastas, bread and biscuits. These enable someone with PKU to expand and "normalise" their restricted diet. However, within the UK these products are only available on prescription. Therefore, to maintain a supply of these foods requires someone to order them regularly from their general practitioner and maintain an on-going relationship with their GP. Unfortunately many practices now are placing a limit on the number of items that can be ordered and supplied, causing frustration to the person with PKU. Also, unlike other well-known chronic conditions, these prescriptions carry a fee - adding a considerable financial burden.

 
The other important aspect of treatment is the phenylalanine free amino acid supplements that must be taken every day. These usually come in the form of liquid drinks. When these supplements were first developed they were foul tasting. Today, manufacturers have worked hard to try and develop more palatable supplements that children and adults will find easier to take. In 2012 the cost of providing these supplements has been estimated at just under £6,000 per year, per person.

 
Everyone with PKU needs to know how much protein and how many phenylalanine free amino acid supplements to take to maintain their blood levels within safe limits. These limits vary throughout their life. For example, women who are trying to conceive or who are pregnant must maintain very low levels, as phenylalanine is teratogenic.
 
Regular blood tests - (finger pricks onto a Guthrie card up to three times a week) - are taken by either the parent or person with PKU and sent to the specialist Inherited Metabolic Disease service to measure the Phenylalanine level in the blood. These results are reviewed by a specialist dietician and discussed with the person with PKU and decisions made on any adjustments to their diet or supplements. It is vital for someone with PKU to maintain this link with the specialist centre, but the need for regular contact, clinic appointments and blood tests can place a burden on their lives.