Gyrate atrophy of the choroid and retina, which is often shortened to gyrate atrophy, is an inherited disorder characterized by progressive vision loss. People with this disorder have an ongoing loss of cells (atrophy) in the retina, which is the specialized light-sensitive tissue that lines the back of the eye, and in a nearby tissue layer called the choroid. During childhood, they begin experiencing nearsightedness (myopia), difficulty seeing in low light (night blindness), and loss of side (peripheral) vision. Over time, their field of vision continues to narrow, resulting in tunnel vision. Many people with gyrate atrophy also develop clouding of the lens of the eyes (cataracts). These progressive vision changes lead to blindness by about the age of 50.

Most people with gyrate atrophy have no symptoms other than vision loss, but some have additional features of the disorder. Occasionally, newborns with gyrate atrophy develop excess ammonia in the blood (hyperammonemia), which may lead to poor feeding, vomiting, seizures, or coma. Neonatal hyperammonemia associated with gyrate atrophy generally responds quickly to treatment and does not recur after the newborn period.

Gyrate atrophy usually does not affect intelligence; however, abnormalities may be observed in brain imaging or other neurological testing. In some cases, mild to moderate intellectual disability is associated with gyrate atrophy.

Gyrate atrophy may also cause disturbances in the nerves connecting the brain and spinal cord to muscles and sensory cells (peripheral nervous system). In some people with the disorder these abnormalities lead to numbness, tingling, or pain in the hands or feet, while in others they are detectable only by electrical testing of the nerve impulses.

In some people with gyrate atrophy, a particular type of muscle fibers (type II fibers) break down over time. While this muscle abnormality usually causes no symptoms, it may result in mild weakness.

Mutations in the OAT gene cause gyrate atrophy. The OAT gene provides instructions for making the enzyme ornithine aminotransferase. This enzyme is active in the energy-producing centers of cells (mitochondria), where it helps break down a molecule called ornithine. Ornithine is involved in the urea cycle, which processes excess nitrogen (in the form of ammonia) that is generated when protein is broken down by the body. In addition to its role in the urea cycle, ornithine participates in several reactions that help ensure the proper balance of protein building blocks (amino acids) in the body. This balance is important because a specific sequence of amino acids is required to build each of the many different proteins needed for the body's functions. The ornithine aminotransferase enzyme helps convert ornithine into another molecule called pyrroline-5-carboxylate (P5C). P5C can be converted into the amino acids glutamate and proline.

OAT gene mutations that cause gyrate atrophy result in a reduced amount of functional ornithine aminotransferase enzyme. A shortage of this enzyme impedes the conversion of ornithine into P5C. As a result, excess ornithine accumulates in the blood (hyperornithinemia), and less P5C than normal is produced. It is not clear how these changes result in the specific signs and symptoms of gyrate atrophy. Researchers have suggested that a deficiency of P5C may interfere with the function of the retina. It has also been proposed that excess ornithine may suppress the production of a molecule called creatine. Creatine is needed for many tissues in the body to store and use energy properly. It is involved in providing energy for muscle contraction, and it is also important in nervous system functioning.

Gyrate atrophy of the choroid and retina is a genetic condition. Babies inherit it from their biological (birth) parents.

• Gyrate atrophy of the choroid and retina is an autosomal recessive condition. Babies inherit the condition when each parent passes down a nonworking OAT gene to their baby. Only babies with two nonworking OAT genes—one from the mom and one from the dad—have this condition.
  • People with one working copy and one nonworking copy of the OAT gene are called carriers.
  • Carriers do not have or develop the condition. However, they may pass down a nonworking copy of the gene to their children.
  • If two parents are carriers of a nonworking copy of the OAT gene, they have a 1 in 4 chance of having a child with Gyrate atrophy of the choroid and retina.
  • Carriers for Gyrate atrophy of the choroid and retina often do not know they are carriers before having a child with the condition. In most cases, families have no history of the condition until the birth of a child with Gyrate atrophy of the choroid and retina.
  • Parents who already have a child with Gyrate atrophy of the choroid and retina still have a 1 in 4 chance of having another child with Gyrate atrophy of the choroid and retina. This 1 in 4 chance stays the same for all future children.
• Genetic counselors and medical geneticists can help families learn about this condition and the chance of having children with it.

The signs of Gyrate atrophy of the choroid and retina usually don’t begin until childhood. In rare cases, newborns may have some symptoms.

Signs of the condition may include the following:

• Nearsightedness (myopia)
• Night blindness
• Loss of side (peripheral) vision
• Clouding of the eyes (cataracts)

Newborn screening for Gyrate atrophy of the choroid and retina requires collecting a small amount of blood from your baby’s heel. Screening measures how much ornithine is in your baby’s blood. Babies with high levels of ornithine might have Gyrate atrophy of the choroid and retina.

What Happens After an Out-of-Range Screening Result?

If your baby’s blood spot screening result for Gyrate atrophy of the choroid and retina is out-of-range, your baby’s health care provider will contact you. Together, you will discuss next steps and follow-up plans.

An out-of-range screening result does not mean that your baby definitely has the condition. It does mean that your baby needs more follow-up testing.

Your baby may need the following tests after an out-of-range screening result:

• Blood and urine tests
• Genetic testing using a blood sample
• Special eye exams

You should complete any recommended follow-up testing as soon as possible. Babies with this condition can develop serious vision problems in childhood if they are not diagnosed and treated quickly.

False-positive newborn screening results for this condition can happen.

Newborn screening helps babies lead healthier lives. If your baby has an out-of-range result, follow up with your health care provider quickly. It is important to follow their instructions. Your baby may need to get treatment right away, even if they are not showing signs or symptoms. In some cases, your baby’s health care provider may decide it is best to watch (monitor) your baby to decide next steps. Careful monitoring and early treatment will help your baby stay as healthy as possible.

It is important to talk to your health care provider about which treatment(s) are best for your baby. The goal of treatment is to prevent the health problems caused by this condition.

Treatments may include the following:

• Diet low in certain proteins
• Vitamins and other supplements
• Vision aids, like eyeglasses

Children who receive early and ongoing treatment for Gyrate atrophy of the choroid and retina can lead healthier lives.