Phenylketonuria And Brain Development

Phenylketonuria (PKU) stands as a rare metabolic disorder that prevents your body from breaking down the amino acid phenylalanine. PKU remains a subject of paramount importance in healthcare and scientific research around the globe. Understanding the mechanisms underlying PKU and its effects on brain development is crucial for planning effective management strategies and improving long-term outcomes for affected people.

In this article, we explore the interesting relationship between PKU and brain development, shedding light on its significance and implications for healthcare professionals, researchers, and those living with this condition.

Understanding phenylketonuria (PKU) 

Amino acids are the basic blocks of protein which are found in food like meat or fish. When there are insufficient enzymes to break down the amino acid, there will be a build up of these amino acids. Enzymes are essential for us to break down large molecules of proteins, carbohydrates and fats into smaller sizes for better digestion. 

The enzyme phenylalanine hydroxylase is absent in the case of PKU, so an unhealthy level of phenylalanine builds up in the body. When there is an excess of the phenylalanine amino acid in your blood and brain, this could eventually cause brain damage. However, this could be prevented by early detection and newborn screening.¹

Impact of phenylalanine on brain development 

Phenylalanine is present in most common foods like meat, fish, potatoes, bread or cheese. It is extremely important for your growth.² Research has been done to try to understand the relationship between how phenylalanine causes brain damage, but there is still not enough conclusive evidence. 

For newborns and toddlers with PKU, it is possible that the faulty formation of synapses, which are the communication points between brain and spinal neurons, during early brain development could be the reason. Neurons are basically messengers in your body that carry and send messages to other neurons through the synapse. Another reason could be the protruding spine of a neuron not properly forming and thus not transmitting signals.³  

Moreover, another study analysed adults aged over 16 and those with high phenylalanine levels had brain development issues and higher symptoms of attention deficit hyperactivity disorder (ADHD), depression, and anxiety. Those who had lower levels of phenylalanine had reported better brain performance like improved reaction time, attention span, and the ability to adapt according to the changing environment.⁴ 

Those with PKU have a greater likelihood of having autism spectrum disorder, Tourette/ tic disorders, eating disorders or poor complex thinking based on research done. In addition, symptoms of extreme tiredness, epilepsy, disturbance of sleep, personality disorders, phobias, migraines and psychosis are elevated in those diagnosed with PKU compared to those without.⁵ 

In another study conducted on 95 patients with PKU and 95 healthy patients, it was concluded that mostly adolescents and adults with PKU had more problems with social skills. They also showed worsened thought processes that influence their social behaviour.⁶  This could cause them to be poor at social situations and interactions, or possibly have autism spectrum disorder as discovered in the previous study. 

From all this information gathered, it is quite clear that there is a relationship between having PKU and declining brain development, which could vary from poor complex thinking to poor social skills.

Management and treatment of PKU 

FAQs

What is the diagnosis of PKU?

Usually, every newborn is tested for PKU, and this can be done by pricking their heel for a blood sample which will be tested at a lab to check the levels of amino acid, which is called a blood spot test. If you are having another baby and your first child has PKU, you should inform your midwife and GP so they can run an early screening blood test after birth in addition to the blood spot test.¹ 

Are there any support groups for PKU?

In the UK, there are peer support groups through the Metabolic Support UK called ‘Metabolic Connect’. As living with PKU can be lonely and scary, these groups connect you with other families and individuals who are going through the same things as you are and are willing to share their experiences. 

Summary

In summary, understanding that PKU could cause worsening brain development such as the inability to pay attention, inability for complex thinking, poor social skills, etc. is hugely significant in managing this disease. Being aware of this could improve adherence and discipline, especially in younger children. 

Parents or carers should teach children with PKU from a young age the importance of eating a low-protein diet and finding a balance as they get older. There should be frequent clinical follow-ups for teenagers and adults at metabolic centres or hospitals.

Although research does advise maintaining low blood phenylalanine throughout your whole life to combat PKU, there are limits in past studies such as the study design, study size and recruiting patients who were treated at a later stage in their life which might not give the best comprehensive results. There are challenges and overcoming these with more evidence could be the breakthrough discovery for those living with PKU.