Phenylketonuria and the Eyes

Phenylketonuria and the Eyes

Phenylketonuria (PKU) is a rare genetic disease that affects the levels of several molecules in the body. The changes in the concentrations of these molecules can affect multiple parts of the body, including the eyes.

Because melanin, the pigment responsible for hair color and skin color, is affected by PKU, those with the disorder often have fair skin, light hair, and blue eyes. People with PKU also may have other eye issues or vision problems.

About PKU

Mutations in the PAH gene cause PKU. This gene contains the information necessary for cells to make an enzyme called phenylalanine hydroxylase (PH).

When there is a mutation in the gene, it leads to reduced levels of functional PH. That enzyme is necessary for the conversion of the amino acid phenylalanine (Phe) into the amino acid tyrosine (Tyr). Of note, amino acids are building blocks of proteins.

Cells can later convert Tyr into neurotransmitters like dopamine, norepinephrine, and epinephrine. Neurotransmitters are molecules that send signals between nerve cells. The lack or decrease in functional PH leads to a lack of Tyr and a buildup of Phe in the body. This ultimately leads to the neurological symptoms of PKU.

How does PKU affect the eyes?

PKU can cause several changes to the eyes. This is especially the case for those who did not receive treatment at an early age.

The most common effects of PKU on the eyes are having blue eyes and hypopigmentation of the fundus — meaning reduced color of the inside of the eye. These two symptoms are related to lower levels of melanin, the pigment which darkens skin, hair, and eyes. Like neurotransmitters, cells produce melanin from Tyr, which has low concentrations in PKU patients.

Some patients with PKU also may have photophobia, which is sensitivity to light. Researchers note that the blue color of the iris absorbing less light and the hypopigmentation of the fundus can cause this common condition.

Cataracts, or cloudiness of the lens of the eye, and corneal opacities, a disorder that results in cloudiness of the cornea, also can occur in people with PKU.

PKU also can cause a decrease in contrast sensitivity, the ability to differentiate between small increments of light, research has shown. Lower levels of dopamine in the eye, which is important in nerve cell signaling in the retina, are likely responsible for this decrease.

A study in a rat model of PKU investigated the effects of elevated levels of phenylalanine on fetuses and young pups. The study found that high maternal levels of Phe lead to reduced thicknesses of the cornea, lens, and retina, and could impair vision in the pups. No similar studies have been done in humans. But it possibly may be helpful if mothers seek to minimize their Phe levels with a goal toward limiting any potential impact on their babies’ vision.

Are there options to improve vision in PKU?

Keeping Phe levels low by reducing or eliminating it from the diet can successfully reduce the effects of PKU. A case study in a PKU patient who started having visual impairment showed that returning to a strict PKU diet cleared up his vision problems.

Despite a low-phenylalanine diet, PKU levels may still stay higher than normal in some patients. A study showed that treatment with sapropterin dihydrochloride (available as Kuvan) reduced Phe levels and eliminated contrast sensitivity deficits in PKU patients.


Last updated: Sept. 24, 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.

How useful was this post?

Click on a star to rate it!

Average rating 5 / 5. Vote count: 2

No votes so far! Be the first to rate this post.

As you found this post useful...

Follow us on social media!

We are sorry that this post was not useful for you!

Let us improve this post!

Tell us how we can improve this post?