Phenylketonuria and Epilepsy

Phenylketonuria and Epilepsy

Seizures are fairly common in people with phenylketonuria (PKU), especially those who are not started on a low phenylalanine (Phe) diet at birth.

What is PKU?

Phenylketonuria (PKU) is a rare genetic disease of amino acid metabolism, due to phenylalanine hydroxylase (PAH) enzymes that don’t work as they should. Mutations in the PAH gene that resides on chromosome 12 cause the disease.

PAH normally converts the amino acid Phe into the amino acid tyrosine (Tyr). The body uses Tyr as the building block for a number of molecules, such as neurotransmitters (chemicals that send messages between nerve cells) and melanin (the pigment that makes skin, hair, and eyes darker).

When the PAH enzyme does not work properly, the body cannot produce Tyr, and Phe accumulates. Excessively high levels of Phe and low levels of Tyr lead to PKU’s symptoms, with varying degrees of severity, in individuals.

What is epilepsy?

Epilepsy is the result of abnormal electrical activity in the brain that can lead to seizures. These seizures can be localized to one area of the brain (focal), or more widespread (generalized). They can cause confusion, altered sensations, loss of consciousness, and loss of body control, evident as stiffening muscles, jerking movements, or falling down.

How can PKU cause epilepsy?

Researchers estimate that as many as 50% of PKU patients experience seizures, with 25% developing generalized seizures.

Although they do not fully understand the exact mechanism relating PKU and seizure activity, evidence supports high Phe levels being toxic to nerve cells, and causing chemical and structural changes in the brain. Phe accumulation is also linked to oxidative stress in cells, and to the formation of amyloid plaques that interfere with brain function. All of these changes can damage nerve cells, and possibly provoke seizures and epilepsy.

Treatment options

PKU currently has only limited treatment options, the most common being the adoption of a special diet that eliminates food sources of Phe. Patients also take a formula to supplement their diet, as they are at risk of not receiving enough protein.

Despite following a strict diet, some patients may still have elevated levels of Phe in their bodies. Two medications, Kuvan (sapropterin dihydrochloride) and Palynziq (pegvaliase-pqpz), can help to control and lower blood levels of Phe as add-on treatments.

Seizures have been reported in PKU patients who stopped adhering to a low Phe diet years earlier.

Patients who experience seizures should consult with their doctors, who may recommend antiepileptic or anticonvulsive medications.


Last updated: Oct. 1, 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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