Disease relevance of Gyrate Atrophy

• This can greatly assist studies of retinal manifestations of diseases, such as gyrate atrophy, retinitis pigmentosa, sickle cell disease, and acquired immune deficiency syndrome [1].
• The diagnosis of hyperornithinemia and gyrate atrophy (HOGA) depends upon the presence of five characteristic features: (1) typical chorioretinal lesions, (2) high myopia, (3) cataracts, (4) hyperornithinemia, and (5) autosomal recessive inheritance [2].
• METHODS: We studied eight patients suffering from different hereditary retinal dystrophies (Best's disease, reticular dystrophy, butterfly-shaped dystrophy, gyrate atrophy, and retinitis pigmentosa) who developed choroidal neovascularization [3].
• Among the disorders reviewed are X-linked retinitis pigmentosa, Norrie's disease, gyrate atrophy and retinoblastoma, and there are also sections on crystallins and visual pigments [4].
• Although similar on ophthalmoscopy, fluourescein angiography, and by electroretinography, the retinal disease in our patient differed from cases of gyrate atrophy of the choroid and retina in having normal plasma ornithine levels [5].

High impact information on Gyrate Atrophy

• Similar results were observed for two nonsense mutations in the gene encoding ornithine delta-aminotransferase from patients with gyrate atrophy [6].
• Cultured fibroblasts from a patient with gyrate atrophy of the retina do not convert L-ornithine, uniformly labeled with carbon-14, to proline [7].
• Gyrate atrophy of the choroid and retina with hyperornithinemia. Deficient formation of guanidinoacetic acid from arginine [8].
• We conclude that in gyrate atrophy patients, formation of guanidinoacetate, creatine, and possibly phosphocreatine is inhibited at the transaminidation step by the high concentrations of ornithine [8].
• Vitamin B6 in management of gyrate atrophy of choroid and retina [9].

Chemical compound and disease context of Gyrate Atrophy

• Gyrate atrophy of the choroid and retina: amino acid metabolism and correction of hyperornithinemia with an arginine-deficient diet [10].
• Pyridoxine-responsive gyrate atrophy of the choroid and retina: clinical and biochemical correlates of the mutation A226V [11].
• Reduced brain creatine in gyrate atrophy of the choroid and retina with hyperornithinemia [12].
• They suggest also that abnormalities of proline metabolism may be involved in the progress of gyrate atrophy [13].
• A 44-year-old woman had a fundus appearance similar to that of gyrate atrophy, a macular lesion, and excessive urinary excretion of proline, hydroxyproline, and glycine [14].

Biological context of Gyrate Atrophy

• Point mutation affecting processing of the ornithine aminotransferase precursor protein in gyrate atrophy [15].
• Exon scanning of the ornithine aminotransferase gene in a gyrate atrophy patient detected and localized a mutation in the sixth exon [16].
• Twenty-nine Finnish patients (8-80 years old during follow-up) with hyperornithinemia and gyrate atrophy (HOGA) were followed 2 to 31 years to determine when and how rapidly visual acuities and visual functions were affected by the disease [17].

Anatomical context of Gyrate Atrophy

• Gyrate atrophy of the choroid and retina: improved visual function following reduction of plasma ornithine by diet [18].
• We measured the activity of ornithine aminotransferase (L-ornithine:2-oxo-acid aminotransferase, EC 2.6.1.13) in phytohemagglutinin-stimulated lymphocytes of a patient with gyrate atrophy and her daughter [19].
• Retrovirus-mediated gene transfer of ornithine-delta-aminotransferase into keratinocytes from gyrate atrophy patients [20].
• We recently showed that ornithine exhibits cytotoxicity to human retinal pigment epithelial (RPE) cell lines treated with the OAT inhibitor, 5-fluoromethylornithine (5-FMOrn), and suggested that this system may be an in vitro model of gyrate atrophy [21].

Gene context of Gyrate Atrophy

• Gyrate atrophy (GA), a recessive eye disease involving progressive loss of vision due to chorioretinal degeneration, is associated with a deficiency of the mitochondrial enzyme ornithine aminotransferase (OATase; ornithine-oxo-acid aminotransferase; L-ornithine:2-oxo-acid aminotransferase, EC 2.6.1.13) with consequent hyperornithinemia [22].
• Gyrate atrophy of the choroid and retina is an autosomal recessive, blinding human disease caused by a deficiency of the mitochondrial matrix enzyme ornithine aminotransferase (OAT) [23].
• To our knowledge, this is the first reported case of FCMD associated with atypical gyrate atrophy of the choroid and retina [24].
• Gyrate atrophy of the choroid and retina is a rare inherited form of chorioretinal degeneration due to a deficiency of ornithine aminotransferase (OAT) [25].
• Hyperornithinemia associated with gyrate atrophy of the choroid and retina in a child with myopia [26].

Analytical, diagnostic and therapeutic context of Gyrate Atrophy

• Reproducing these mutations by site-directed mutagenesis and expressing the mutant ornithine delta-aminotransferase in Chinese hamster ovary cells confirms that several of these mutations inactivate ornithine delta-aminotransferase and cause gyrate atrophy in these patients [27].
• A sensitive and convenient radioisotopic assay for ornithine aminotransferase (OAT) and an enzyme immunoassay for human ornithine aminotransferase were developed for studying decrease in activity of this enzyme in gyrate atrophy of the choroid and retina with hyperornithinemia [28].
• Clinical trials of vitamin B6 and proline supplementation for gyrate atrophy of the choroid and retina [29].
• Ornithine-delta-amino transferase-deficient mice were produced by gene targeting in the hope of creating an animal model for gyrate atrophy [30].

References