gyrate atrophy

Gyrate Atrophy: A Rare Genetic Disorder

Gyrate atrophy is a rare, inherited retinal dystrophy characterized by progressive chorioretinal degeneration, early cataract formation, and myopia. It is caused by a deficiency in the enzyme ornithine aminotransferase (OAT), which results in a 10- to 20-fold increase in plasma ornithine concentrations [10][11].

Key Features:

• Progressive vision loss: Due to deterioration of the retina and choroid in the eye [9]
• Chorioretinal degeneration: Affecting the layers of the retina and choroid, leading to progressive loss of cells [5][6]
• Early cataract formation: A common sign associated with gyrate atrophy [10]
• Myopia: A type of nearsightedness caused by elongation of the eyeball [2]

Inheritance Pattern:

Gyrate atrophy follows an autosomal recessive pattern of inheritance, meaning that only individuals who have two copies of the mutated OAT gene (one from each parent) are affected. People with only one mutated gene copy are known as "carriers" and are not affected by the condition but may pass the faulty gene copy to their children [13].

Causes:

The deficiency in ornithine aminotransferase (OAT) enzyme leads to an increase in plasma levels of ornithine, which is thought to result in the ocular symptoms associated with gyrate atrophy [11][12]. Research into the disease includes investigating how variant mutations of the alleles affect OAT function and exploring potential treatments [14].

References:

[1] - Elevated levels of systemic ornithine and genetic sequencing confirm the diagnosis. [2] - Gyrate atrophy may also cause disturbances in the nerves connecting the brain and spinal cord to muscles and sensory cells (peripheral nervous system). [3] - Gyrate atrophy of the choroid and retina is a rare autosomal recessive metabolic disorder caused by biallelic variants in the OAT gene. [4] - Gyrate Atrophy follows an autosomal recessive pattern of inheritance and only affects individuals who have two copies of the mutated OAT gene, one from each parent.

Progressive Vision Loss

Gyrate atrophy is characterized by progressive vision loss, which is the most common symptom of this condition [2]. This vision loss is due to deterioration of the retina and choroid in the eye [2].

Other Signs and Symptoms

In addition to progressive vision loss, other signs and symptoms of gyrate atrophy may include:

• Nearsightedness (Myopia): Many people with gyrate atrophy develop nearsightedness, which is a condition where close objects are seen clearly but distant objects appear blurry [3][4].
• Difficulty Seeing in Low Light: People with gyrate atrophy may experience difficulty seeing in low light conditions, also known as night blindness [3][4].
• Loss of Peripheral Vision: Gyrate atrophy can cause loss of peripheral vision, resulting in tunnel vision [2][3].
• Cataracts: Clouding of the lens of the eye (cataracts) is a common symptom of gyrate atrophy [9][10].
• Blindness: In advanced cases, gyrate atrophy can lead to blindness [9].

Early Signs

In rare cases, newborns may have some symptoms of gyrate atrophy, and signs of the condition may include nearsightedness, night blindness, and loss of peripheral vision [3]. These symptoms typically develop during childhood [4][5].

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Diagnostic Tests for Gyrate Atrophy

Gyrate atrophy, a rare autosomal recessive retinal dystrophy, can be diagnosed through various tests that help confirm the presence of mutations in the OAT gene and elevated plasma ornithine levels.

• Biochemical testing: This involves measuring the levels of ornithine in blood, urine, spinal fluid, and aqueous humor. Elevated levels (10-20 times higher than normal) are indicative of gyrate atrophy [8][10].
• Genetic testing: Molecular genetic testing can confirm the presence of mutations in the OAT gene, which is responsible for the deficiency of ornithine aminotransferase [6][12].
• Newborn screening: Some newborn screening procedures also test for gyrate atrophy by collecting a small amount of blood from the baby's heel [7].
• Imaging studies: Retinal imaging can show lesions and areas of atrophy in the retina, which can be used to support a diagnosis of gyrate atrophy [13][14].

These diagnostic tests are essential in confirming the presence of gyrate atrophy and ruling out other retinal disorders. A definitive diagnosis involves integrating clinical features, biochemical testing results, and genetic testing.

References: [6] Clinical Genetic Test offered by Intergen for conditions (1): Ornithine aminotransferase deficiency; Testing genes (1): OAT (10q26.13); Methodology includes ... [7] Sep 15, 2024 — Newborn screening for Gyrate atrophy of the choroid and retina requires collecting a small amount of blood from your baby's heel. To learn more ... [8] In gyrate atrophy, ornithine concentration is increased 10- to 15-fold above normal in all body fluids with concomitant overflow ornithinuria . [10] Diagnosis. Gyrate Atrophy of the choroid and the retina is largely a clinical diagnosis based on history and examination. ... Laboratory Tests. Levels of ornithine have been reported to be 10 to 20 times higher than normal in plasma, urine, spinal fluid, and aqueous humor. [12] Genetic Testing: Molecular genetic testing can confirm the presence of mutations in the OAT gene. [13] (C and D) of the right and left eyes of an 89-year-old woman with a diagnosis of gyrate atrophy. It can be seen how the areas of atrophy in the retinography correspond to hypofluorescent areas in the autofluorescence, and how the preserved areas show ... [14] Retinal images can show the lesions. Other testing can show levels of electrical activity, peripheral vision, night vision among other things. But the diagnosis of gyrate atrophy is confirmed by a blood test showing high levels (10-20 times) of ornithine and/or a genetic test showing a mutation in the OAT gene.

Current Drug Treatments for Gyrate Atrophy

Gyrate atrophy, a rare genetic disorder, has no curative treatment, but several therapeutic modalities aim to slow its progression by targeting different steps within the ornithine pathway. Here are some drug treatments that have been explored:

• Low Arginine Diet: A low-arginine diet has been prescribed to reduce arginine levels in patients with gyrate atrophy. This approach aims to decrease the accumulation of ornithine, which is thought to contribute to the disease's progression (3).
• Topical Non-Steroidal Anti-Inflammatory Drugs (NSAIDs): One patient has been treated with low doses of topical NSAIDs, resulting in favorable outcomes (4). However, this treatment approach may not be suitable for all patients.
• Gene Therapy: Gene therapy and cell replacement therapy are being explored as potential treatments for gyrate atrophy (6).
• Bevacizumab: Bevacizumab has been used to treat intraretinal cystic spaces in a patient with gyrate atrophy of the choroid and retina (14).

Standard Care Treatment

The current standard care treatment for gyrate atrophy is an arginine-restricted diet, which aims to reduce arginine levels and slow disease progression (7). However, it's essential to note that this approach may not be effective for all patients.

References:

• [3] McInnes, R. R. (1980) - Two patients with gyrate atrophy have been treated with a low-arginine diet.
• [4] Piozzi et al. (2017) - One patient has been treated with low doses of topical NSAIDs with favorable outcomes.
• [6] BergenArthur, A. (2023) - Gene therapy and cell replacement therapy are being explored as potential treatments for gyrate atrophy.
• [7] The current standard care treatment of gyrate atrophy is an arginine-restricted diet.
• [14] Bevacizumab has been used to treat intraretinal cystic spaces in a patient with gyrate atrophy of the choroid and retina.

Differential Diagnoses for Gyrate Atrophy

Gyrate atrophy (GA) is a rare autosomal recessive retinal dystrophy that can be challenging to diagnose due to its similarities with other eye conditions. The differential diagnoses for GA include:

• Choroideremia: A genetic disorder characterized by progressive degeneration of the choroid and retina, leading to visual impairment.
• Retinitis Pigmentosa (RP): A group of inherited disorders that cause progressive vision loss due to degeneration of the retina.
• Myopic Degeneration: A condition associated with high myopia, where the retina undergoes atrophy and thinning.
• Cobblestone Degeneration: A rare condition characterized by a distinctive "cobblestone" appearance of the retina.

These conditions can be difficult to distinguish from GA based on clinical presentation alone. Therefore, a comprehensive diagnostic workup is essential to confirm the diagnosis of GA.

Key Diagnostic Features

To differentiate GA from other retinal dystrophies, clinicians should look for the following key features:

• Elevated plasma ornithine levels: A hallmark of GA due to deficiency of the enzyme ornithine ketoacid aminotransferase.
• Progressive chorioretinal degeneration: Characterized by atrophy and thinning of the choroid and retina.
• Hyperpigmented fundi with lobular loss of RPE and choroid: A distinctive feature of GA, particularly in the periphery.

Molecular Genetic Testing

The diagnosis of GA can be confirmed through molecular genetic testing of the OAT gene. This test is essential for distinguishing GA from other retinal dystrophies and for providing a definitive diagnosis.

References:

• [4] Gyrate atrophy of the choroid and retina is a rare autosomal recessive retinal dystrophy caused by a deficiency in ornithine aminotransferase (OAT), leading to elevated plasma ornithine levels.
• [5] Differential diagnoses for gyrate atrophy include choroideremia, retinitis pigmentosa, myopic degeneration, and cobblestone degeneration.
• [15] Gyrate atrophy is part of the differential diagnosis of choroideremia, characterized by hyperpigmented fundi with lobular loss of RPE and choroid starting in the periphery.