PKU & The Brain

Theories for elevated Phe levels altering brain function in PKU 

PKU is characterized by elevated blood levels of the amino acids, phenylalanine (Phe), which is mainly obtained from eating proteins. The symptoms of PKU almost exclusively concern the brain, so it is important to know how high Phe affects your brain.

The brain is protected by a surrounding layer called the blood-brain barrier (BBB), which allows some materials to cross into the brain while preventing the entry of others. The brain needs certain material to cross the BBB to enable normal function. Some of the raw materials that the brain requires are amino acids, including Phe, for building brain proteins and making chemical messengers called neurotransmitters.

Phe and other amino acids use transporters to get across the BBB and into the brain. The number of transporters available is limited, and so there is a constraint on the number and amount of amino acids that can cross the BBB into the brain. If too much of one amino acid is crossing the BBB, it means that others are not able to get through.

In a person with PKU, too much Phe and not enough of the other amino acids are crossing the BBB. This results in increased and toxic Phe levels in the brain and a deficiency of other essential amino acids necessary for the brain to function properly.

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Cognitive, psychological, and behavioral assessment-based evidence for altered brain function in PKU

Psychologists, psychiatrists, and sociologists are researching whether people who maintain a low-Phe diet to keep their blood Phe levels within the recommended range still experience changes in the brain as children, teenagers, and adults.

Blood Phe levels and IQ

Maintaining a Phe-restricted diet and blood Phe levels within the recommended range throughout one’s life will generally result in a normal IQ for people with PKU.

A medical study examined 57 people with PKU with well-controlled Phe levels who were between the ages of 19 and 41. The study assessed these participants for their IQ and attention and information-processing abilities, and compared the results to those of 46 people who did not have PKU. This study showed that people with PKU who had had higher Phe levels during their childhood and teen years had a lower IQ than those with PKU who had had better maintained Phe levels and those who did not have PKU. [Weglage et al. 2013]

Diet therapy and psychological and emotional changes

Research in 2014 is also looking at whether more subtle psychological and emotional changes occur in PKU patients who adhere to diet therapy.

Researchers are looking at links between diet-controlled PKU and executive function. Executive function (EF) is the deliberate, conscious control over your own thoughts, actions, and emotions. Some of the many characteristics of people with EF difficulties include disorganization, being easily frustrated, and poor judgment. Some studies have shown evidence of EF difficulties in people with diet-controlled PKU, while other studies have shown none. Researchers are aiming to conduct a large-scale, long-term study on EF in PKU in order to gain a more accurate understanding of this relationship.

Do you think you have challenges with executive functioning skills?
See our tips sections for help.

Researchers are also studying how quickly people with PKU can react to incoming information, process it, understand it, and use it. This is known as information processing speed. Scientists measure it by setting a variety of tasks with certain time limits and asking people to work on these tasks. People who have difficulties with information processing speed might need longer to start and complete complex tasks and they may appear to struggle with them.

More data is required to determine if information processing speed is affected in those who have diet-controlled PKU. However, the results of one study suggest that if one stays within the current blood Phe range for their age group, information processing speed is not affected.

Scientists are analyzing learning disabilities and problems with academic performance in people with PKU. As of 2014, study results show that math skills may be affected in some individuals with PKU. However, these are small studies and not conclusive.

Do you think you have issues with processing speed?
See our tips sections for help

Studies show that the chemical brain imbalances that have been found in people with PKU are similar to those found in children with attention deficit hyperactivity disorder (ADHD). Symptoms of ADHD fall into one of three large categories:

  • Inattention (inability to concentrate)
  • Hyperactivity
  • Impulsivity

Using standardized criteria for diagnosing ADHD, researchers have found that people who have PKU are more likely to have ADHD or symptoms of ADHD than people who do not. Only a handful of studies have taken place, so more research is required to understand the possible link between PKU and ADHD.

Do you think you experience ADHD-like symptoms?
See our tips sectiona for help

Research has shown that some PKU patients experience psychiatric symptoms that include (but are not limited to) anxiety, depressed moods, and phobias. However, studies examining whether psychiatric disorders occur more frequently in people who have PKU than in those who do not have shown no significant difference between the groups. One robust study of adults with PKU showed that higher blood Phe levels were associated with increased self-reported incidences of depression and fatigue.

Do you think you have issues with psychiatric symptoms? See our psychological assessments section for more information. Remember: you aren’t alone!]

More psychological research is needed to determine the nature and frequency of any problems that may be occurring at a higher rate for people with PKU who adhere to their recommended blood Phe targets than for people who do not have PKU. However, what is clear is that higher blood Phe levels do correlate strongly with many of the psychological and behavioral symptoms observed.

High Phe levels make me irritated, forgetful, and extremely foggy.

Adult with PKU who wished to remain anonymous