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.
Original language | English (US) |
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Pages (from-to) | 191-197 |
Number of pages | 7 |
Journal | Ophthalmic genetics |
Volume | 44 |
Issue number | 2 |
DOIs | |
State | Published - 2023 |
Keywords
- Retinal dystrophy
- arginine
- choroidal dystrophy
- ellipsoid zone
- gyrate atrophy
- inborn errors of metabolism
- low protein diet
- optical coherence tomography
ASJC Scopus subject areas
- Genetics(clinical)
- Ophthalmology
- Pediatrics, Perinatology, and Child Health