Gyrate atrophy of the choroid and retina is a rare inherited disorder that causes progressive vision loss. This condition affects the choroid, a vascular layer, and the retina, the light-sensitive tissue. Over time, the cells in these ocular structures slowly break down, leading to a gradual decline in sight. It is a metabolic disease, involving disruptions in the body’s chemical processes.
Genetic Origins and Ornithine Metabolism
Gyrate atrophy is an autosomal recessive disorder, meaning an individual must inherit two copies of a mutated gene, one from each parent, to develop the condition. The specific gene involved is OAT, located on chromosome 10q26. This gene provides the instructions for making an enzyme known as ornithine aminotransferase (OAT).
The ornithine aminotransferase enzyme plays a role in breaking down the amino acid ornithine. When mutations occur in the OAT gene, the enzyme becomes deficient or entirely absent. This deficiency prevents the proper breakdown of ornithine, causing it to accumulate to high levels in the blood and other bodily fluids, including those within the eye. Ornithine levels in affected individuals can be 10 to 20 times higher than those found in healthy individuals. This excessive accumulation of ornithine is thought to be toxic, particularly to the specialized cells of the retina and choroid, leading to their degeneration.
Symptoms and Vision Progression
The symptoms of gyrate atrophy typically begin in late childhood or adolescence, although the age of onset can vary. Patients often first notice difficulty seeing in dim light, known as night blindness. Increasing nearsightedness, or myopia, is also a common early manifestation.
As the condition progresses, individuals experience a gradual loss of their peripheral vision. This progressive narrowing of the visual field often results in what is described as “tunnel vision.” Over time, the areas of atrophy in the retina expand and coalesce, eventually affecting central vision, which is necessary for tasks like reading and recognizing faces. Many individuals with gyrate atrophy also develop cataracts, a clouding of the eye’s lens, often at an earlier age than typically seen. This combination of progressive vision changes can lead to severe vision impairment or blindness, commonly occurring between 40 and 55 years of age.
Diagnostic Process
A comprehensive eye examination is a primary step, where an ophthalmologist will carefully assess visual acuity and peripheral vision. During a dilated fundus examination, the doctor can observe characteristic patchy, circular areas of chorioretinal atrophy in the peripheral retina, often with distinct borders and visible underlying choroidal vessels.
Blood tests are also performed to measure the levels of ornithine in the plasma. Unusually high concentrations of ornithine, typically 10 to 20 times above normal, are a strong indicator of the condition. Finally, genetic testing can be conducted to identify specific mutations in the OAT gene, offering a definitive confirmation of gyrate atrophy.
Management and Treatment Approaches
The primary approach to managing gyrate atrophy and slowing its progression involves dietary modifications. An arginine-restricted diet is implemented because arginine is a precursor amino acid from which ornithine is formed in the body. By limiting the intake of arginine, the diet aims to reduce the overall production of ornithine, thereby lowering its circulating levels in the blood. This dietary intervention can help stabilize ornithine levels and has been shown to slow the progression of retinal degeneration and improve some visual outcomes.
Adhering to a strict arginine-restricted diet can be challenging, as arginine is present in most natural proteins. Patients require careful guidance from dietitians to ensure adequate nutrition while minimizing arginine intake. Regular monitoring of blood ornithine levels is necessary to adjust the diet as needed and ensure its effectiveness.
Another management strategy involves supplementation with vitamin B6. This vitamin acts as a co-factor for the ornithine aminotransferase enzyme. In a subset of patients, particularly those with certain OAT gene mutations, vitamin B6 supplementation can help improve the residual function of the enzyme, leading to a reduction in ornithine levels. The response to vitamin B6 varies among individuals, so its effectiveness is assessed on a case-by-case basis. Regular follow-up with ophthalmologists is also important to monitor vision changes and manage associated complications, such as cataracts, which can be treated with surgical removal to improve sight.