Novel Insights Into Gyrate Atrophy of the Choroid and Retina (GACR): A Cohort Study

Abstract: Gyrate atrophy of the choroid and retina (GACR, OMIM #258870) is a rare inherited metabolic disorder characterized by progressive chorioretinal degeneration and hyperornithinemia. Current therapeutic modalities potentially slow disease progression but are not successful in preventing blindness. To allow for trial development, increased knowledge of the clinical phenotype and current therapeutic outcomes is required. In this study, we analyzed 27 patients with GACR. The median age at inclusion was 24years (range 8–58), with a median age at diagnosis of 14years (range 0–42). Symptoms began at a mean age of 9years (range 0–21). Mixed-models analysis showed a significant association between dietary natural protein intake and plasma ornithine levels. Ornithine increase significantly with age, independent of dietary natural protein intake. We found no statistically significant association between ornithine levels and best-corrected visual acuity over time. Patients who started a natural protein-restricted diet below 10years of age had better VF outcomes compared to patients that started at a later age. MR spectroscopy was used to asses cerebral creatine deficiency, which was present in 15/20 patients, of whom 10 were supplemented with creatine at the time. Finally, using the Michigan Retinal Degeneration Questionnaire, we provided a first insight into the vision-related disability reported by patients with GACR and showed that higher foveal sensitivity was associated with less perceived disability. To conclude, this study provides insights into the phenotype, genotype, biochemistry, and treatment effects of GACR, which can be used for care pathways and clinical trial design.

Link to article: https://pmc.ncbi.nlm.nih.gov/articles/PMC11703598/

PubMed:  https://pubmed.ncbi.nlm.nih.gov/39761806/

Authors: Berith M. Balfoort, Filip Van den Broeck, Camiel J. F. Boon, Martijn C. G. J. Brouwers, Roselie M. H. Diederen, Preet Dhillon, GACR “Bird’s Eye View” Consortium, Peter M. van Hasselt, Bregje Jaeger, Jessica S. Karuntu, Alexander J. M. Rennings, Francjan J. van Spronsen, Corrie Timmer, Margreet A. E. M. Wagenmakers, Julie De Zaeytijd, Bart P. Leroy, Andreas Schulze, Clara D. van
Karnebeek, Marion M. Brands

Key Terms: Non-CCDS Disease, Supplements, MRS, Diagnostic, Clinical Study, Basic Science, Adult Patient, Pediatric Patient