PKU & The Brain

People with PKU, especially those with Phe levels above the recommended range, often report feeling depressed, anxious, and agitated. Medical studies have shown that people with PKU are more likely to be depressed and anxious, and to suffer from phobias and reduced positive emotions and achievement. Adults and teenagers with PKU who have been treated early and continuously with a low-Phe diet may still experience mild neurocognitive issues or symptoms. You may have experienced these without recognizing it as a part of your PKU.

These symptoms and issues can worsen if the low-Phe diet is not followed. As your Phe levels go up, your behavior may change. You may experience mood swings and feel agitated. Your friends and family may report that you act differently—they may even describe the behavior as irritating.

When I was off diet I was diagnosed with aniexty and night terrors...I did some research and what I learned from attending the NPKUA conference and reviewing my medical records was that the anxiety I experianced as a teen was very likely due to being off diet and having high Phe levels.

Kay, 56 years old

In order to help deal with such symptoms, it’s important that you understand what may be causing them. Research shows that getting your blood Phe levels back under control will help you regain control over these symptoms you may be experiencing. Doctors and dietitians, as well as adults with PKU who have dealt with these issues, have provided some tips on controlling Phe levels and dealing with the related psychological or neurological issues.

Understanding the relationship between Phe levels and neurocognitive symptoms may help encourage you to maintain your Phe levels within the recommended range of 120–360 μmol/L (2–6 mg/dL).

Physical evidence for altered brain function in PKU

Scientists are studying whether the current standard therapy that involves a Phe-restricted diet and meeting blood Phe targets can still lead to changes in the brain.

Brain scans and white matter

Some of the physical evidence scientists have gathered involves brain scans. So far, the evidence shows that a large percentage of people with PKU may have some visible brain abnormalities, even when on diet. There is a reasonable correlation between the amount of brain abnormalities and lifetime Phe levels: the higher the Phe levels, the more brain abnormalities appear.

Evidence from MRIs has revealed that the majority of people with PKU have abnormalities with the white matter in their brain. A medical study examined the MRIs and IQ of 57 people aged 19 to 46 years old who had PKU. The study compared these test results with those of 46 people of the same age range who did not have PKU.  In the PKU group, 96% had white matter abnormalities commonly associated with PKU that were not experienced by the people who did not have PKU. The IQ scores in the PKU group were lower than the group that did not have PKU, especially in those cases where high Phe levels had been experienced during childhood and the teen years.

Some researchers think that these changes in white matter may cause problems in how fast a person can process information.

More research is needed to understand the nature and impact of these abnormalities as seen in brains scans of patients with diet-controlled PKU.


Another form of physical evidence has shown that people with PKU may have lower levels of certain brain chemicals called neurotransmitters.

The enzyme phenylalanine hydroxylase (PAH) has the job of changing some of the Phe a person consumes into a different amino acid, called tyrosine (Tyr), which is used to make the brain neurotransmitter called dopamine.

Evidence suggests that changes in PAH function in people with PKU can result in lower amounts of dopamine in the brain.

Some symptoms of low dopamine include drastic mood swings, difficulty paying attention, and sleep disturbances.

More data is necessary to make any conclusions based on this research.

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