Behavioral Problems in Children With Phenylketonuria

Behavioral Problems in Children With Phenylketonuria

Children with phenylketonuria (PKU) often exhibit behavioral problems. The information that follows includes details about the different behavioral problems and possible reasons for them in children with PKU.

What is PKU?

PKU is a rare genetic disorder caused by mutations in the PAH gene. These mutations lead to a reduction in the amount of functional phenylalanine hydroxylase (PAH) enzyme. This enzyme normally converts the amino acid phenylalanine (Phe) into another amino acid called tyrosine (Tyr). The body uses Tyr to make several other molecules, including dopamine, serotonin, and melanin. Without enough functional PAH enzyme, Phe builds up in the body. Then Tyr levels drop, affecting the amounts of dopamine, serotonin, melanin.

Behavioral problems in children

The behavioral issues that children with PKU experience depend on the severity of their disease and whether they followed a Phe-restricted diet from an early age.

Children with no dietary restriction

Children with PKU who did not follow a strict low Phe diet may have several behavioral issues. These may include hyperactivity, stereotypy (repeated movements for no reason), and anxiety. They also may show signs of autism and aggressive behavior.

Children on a low Phe diet

Patients who were identified at birth and started on a low Phe diet at an early age do not experience some of the more serious symptoms of PKU such as intellectual disability. However, these patients still tend to have Phe levels in their bodies that are too high. These high Phe levels seem to correlate with more subtle behavioral issues, such as low motivation to achieve, low self-esteem, problems in school, and attention problems. These children also may have difficulty with executive function tasks. These are tasks that involve control over your own thoughts, actions, and emotions, such as reasoning, attention, impulse control, and mental flexibility. Trouble with executive function can cause difficulty adapting to changes, apathy, poor judgment, and little resistance to frustration.

How does PKU cause behavioral problems?

The underlying mechanisms of how PKU can cause behavioral issues are not clear. Researchers think that the high levels of Phe and resulting decreases in dopamine cause changes in the brain. Dopamine is important for the normal function of a region in the brain called the prefrontal cortex, which is tied to executive functions.

How doctors treat behavioral problems

The first step to treating PKU-related behavioral problems, and PKU in general, is to make sure the patient is on a strict Phe-reduction diet.

In addition to a strict diet, patients also may benefit from medications such as Kuvan. Kuvan helps any remaining PAH enzymes break down Phe in the body.

Enzyme replacement therapy with Palynziq also can help reduce Phe levels in the body.

It also may be helpful for patients and their families to undergo counseling to learn ways to modify and adapt to the child’s behavior.


Last modified: Oct. 7, 2020


Phenylketonuria News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.

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