Gyrate atrophy of choroid and retina

Alternate Names

Ornithine aminotransferase deficiency; Ornithine ketoacid aminotransferase deficiency; Gyrate atrophy; OAT deficiency; OKT deficiency; Hyperornithinemia with gyrate atrophy of choroid and retina; HOGA; Girate atrophy of the retina; Hyperornithinemia; Hyperornithinemia-gyrate atrophy of choroid and retina syndrome; Fuchs atrophia gyrata chorioideae et retinae

Summary

Gyrate atrophy of the choroid and retina is an inherited disorder of protein metabolism characterized by progressive vision loss.

Epidemiology

More than 150 individuals with gyrate atrophy have been identified; approximately one third are from Finland.

Cause

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.

Inheritance

Autosomal recessive inheritance, a 25% chance

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Signs and symptoms

• 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.
• For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed.

80%-99% of people have these symptoms

• Chorioretinal atrophy
• Hyperornithinemia(High blood ornithine levels)
• Myopia(Close sighted)
• Progressive visual loss(Progressive loss of vision)

30%-79% of people have these symptoms

• Abnormal macular morphology
• Aminoaciduria(High urine amino acid levels)
• Blindness
• Chorioretinal hyperpigmentation
• Constriction of peripheral visual field(Limited peripheral vision)
• Progressive night blindness
• Subcapsular cataract

5%-29% of people have these symptoms

• Abnormal hair morphology(Abnormality of the hair)
• Hearing impairment(Deafness)
• Seizure

Diagnosis

• Upon clinical suspicion, diagnostic testing will often consist of measurement of amino acid concentrations in plasma, in search of a significantly elevated ornithine concentration. Measurement of urine amino acid concentrations is sometimes necessary, particularly in neonatal onset cases to identify the presence or absence of homocitrulline for ruling out ornithine translocase deficiency (hyperornithinemia, hyperammonemia, homocitrullinuria syndrome, HHH syndrome).
• Ornithine concentrations can be an unreliable indicator in the newborn period, thus newborn screening may not detect this condition, even if ornithine is included in the screening panel. Enzyme assays to measure the activity of ornithine aminotransferase can be performed from fibroblasts or lymphoblasts for confirmation or during the neonatal period when the results of biochemical testing is unclear.
• Molecular genetic testing is also an option.

Treatment

Treatment may include dietary supplements and/or a specialized diet.

See also

• Eyewiki

Latest articles - Gyrate atrophy of choroid and retina

• Most recent articles
• Ongoing trials

NIH genetic and rare disease info

• NIH info on Gyrate atrophy of choroid and retina

Gyrate atrophy of choroid and retina is a rare disease.