Deficit of human ornithine aminotransferase in gyrate atrophy: Molecular, cellular, and clinical aspects

Gyrate Atrophy (GA) of the chomid and retina (MIM# 258870) is an autosomal recessive disorder due to mutations of the OAT gene encoding ornithine-delta-aminotransferase (OAT), associated with progressive retinal deterioration and blindness. The disease has a theoretical global incidence of approximately 1:1,500,000. OAT is mainly involved in ornithine catabolism in adults, thus explaining the hyperornithinemia as hallmark of the disease. Patients are treated with an arginine-restricted diet, to limit ornithine load, or the administration of Vitamin B6, a precursor of the OAT coenzyme pyridoxal phosphate. Although the clinical and genetic aspects of GA are known for many years, the enzymatic phenotype of pathogenic variants and their response to Vitamin B6, as well as the molecular mechanisms explaining retinal damage, are poorly clarified. Herein, we provide an overview of the current knowledge on the biochemical properties of human OAT and on the molecular, cellular, and clinical aspects of GA.

Automated summary

Gyrate Atrophy is a rare genetic disorder caused by mutations in the OAT gene, leading to progressive retinal degeneration and blindness. Current treatment options include an arginine-restricted diet to limit ornithine load or supplementation with Vitamin B6.