A possible ocular biomarker for response to hyperornithinemia in gyrate atrophy: the effect of pyridoxine, lysine, and arginine-restricted diet in a patient with advanced disease. (4th March 2023)

• Record Type: Journal Article
• Authors: da Palma, Mariana Matioli; Ku, Cristy; Igelman, Austin D.; Burr, Amanda; Shevchenko Sutherland, Liliya; Koerner, Celide; Valle, David; Pennesi, Mark E.; Yang, Paul
• Is Part Of: Ophthalmic genetics. Volume 44:Number 2(2023)
• Page Start: 191
• Page End: 197
• Publication Date: 2023-03-04
• Subjects: Retinal dystrophy -- choroidal dystrophy -- gyrate atrophy -- inborn errors of metabolism -- low protein diet -- arginine -- ellipsoid zone -- optical coherence tomography; Eye -- Diseases -- Genetic aspects -- Periodicals; Eye Diseases -- genetics -- Periodicals; Eye Diseases -- in infancy & childhood -- Periodicals; 617.7
• DOI: 10.1080/13816810.2022.2098986
• Languages: English
• ISSNs: 1381-6810

Abstract

ABSTRACT: Background: Loss of function variants in the ornithine aminotransferase ( OAT) gene cause accumulation of ornithine levels, leading to gyrate atrophy. The benefit of ornithine-lowering therapies has been documented in a mouse model and young patients, however, the effect in adults with advanced disease has not been well described. Materials and Methods: Case report of an adult patient with advanced gyrate atrophy, who underwent treatment with pyridoxine and an arginine-restricted diet for four years. Results: A 51-year-old female with advanced chorioretinal degeneration presented with hyperornithinemia (961 vs. normal 18–135 µmol/L) and compound heterozygous pathogenic variants in OAT (p.Tyr299* and p.Ala270Pro). Treatment with pyridoxine and arginine-diet restriction yielded a maximal reduction in ornithine levels by 71% (275 µmol/L). Optical coherence tomography (OCT) showed a reduction in ellipsoid zone (EZ) thickness that correlated with lower ornithine levels and reversed with higher ornithine levels. While her best-corrected visual acuity remained unchanged, the progressive decline in her visual fields appeared to stabilize during a one-year period when ornithine levels were below 500 µmol/L. Conclusions: In this report, we demonstrate that chorioretinal degeneration appears to stabilize in an adult patient with gyrate atrophy in association with a partial reduction in ornithine levels. We also observed a correlation with reduced EZ thickness on OCT and propose this may be a novel biomarker for ornithine reduction therapies. Our case study characterizes the potential retinal structure-function benefits of ornithine-lowering treatments even in cases of advanced chorioretinal degeneration. Thus, we recommend a low threshold for treating all patients with gyrate atrophy.