Dan Heller1, Chen Weiner2,3, Iris Nasie2, Yair Anikster3,4, Yuval Landau3,4, Tal Koren2, Russell Pokroy1, Adi Abulafia1,3, Eran Pras1,2,3. 1. a Ophthalmology Department , Assaf Harofeh Medical Center , Zerifin , Israel. 2. b Matlow's Ophthalmogenetic Laboratory, Assaf Harofeh Medical Center , Zerifin , Israel. 3. c Sackler Faculty of Medicine , Tel Aviv University , Tel Aviv , Israel. 4. d Metabolic Diseases Unit, Edmond and Lily Safra Children's Hospital , Sheba Medical Center , Tel-Hashomer , Israel.
Abstract
PURPOSE: This study reports the presentation of two families with gyrate atrophy (GA). The aim of this study was to characterize the potential effect of therapeutic regimens on macular edema. METHODS: Two unrelated patients with GA were studied for the potential effect of low protein diet (≤ 0.8 g/kg/d), and oral administration of pyridoxine (500 mg/day), on serum ornithine levels, best corrected visual acuity (BCVA), slit-lamp, OCT, and auto-fluorescence findings. Blood samples for DNA, mRNA, and exons of the OAT gene were screened for mutations and splicing effect when relevant. RESULTS: At presentation, both patients manifested typical ophthalmic features of GA including cystoid macular edema (CME). One patient also exhibited optic nerve head hamartoma. Following treatment ornithine levels have lessened, BCVA improved, and central macular thickness (CMT) markedly decreased in all four studied eyes. The molecular pathologic features included a novel splice site mutation (c.900+1G>A). CONCLUSIONS: We have identified a novel mutation and two formerly described mutations in patients with GA. Of them, one patient comprised an unusual phenotype including bilateral astrocytic hamartomas. We have recognized for the first time improvement in CME following treatment with low protein intake and pyridoxine supplement. This finding may have significance in the understanding of treatment options for macular edema regardless of underlying etiology.
PURPOSE: This study reports the presentation of two families with gyrateatrophy (GA). The aim of this study was to characterize the potential effect of therapeutic regimens on macular edema. METHODS: Two unrelated patients with GA were studied for the potential effect of low protein diet (≤ 0.8 g/kg/d), and oral administration of pyridoxine (500 mg/day), on serum ornithine levels, best corrected visual acuity (BCVA), slit-lamp, OCT, and auto-fluorescence findings. Blood samples for DNA, mRNA, and exons of the OAT gene were screened for mutations and splicing effect when relevant. RESULTS: At presentation, both patients manifested typical ophthalmic features of GA including cystoid macular edema (CME). One patient also exhibited optic nerve head hamartoma. Following treatment ornithine levels have lessened, BCVA improved, and central macular thickness (CMT) markedly decreased in all four studied eyes. The molecular pathologic features included a novel splice site mutation (c.900+1G>A). CONCLUSIONS: We have identified a novel mutation and two formerly described mutations in patients with GA. Of them, one patient comprised an unusual phenotype including bilateral astrocytic hamartomas. We have recognized for the first time improvement in CME following treatment with low protein intake and pyridoxine supplement. This finding may have significance in the understanding of treatment options for macular edema regardless of underlying etiology.
Authors: Adrian Dockery; Kirk Stephenson; David Keegan; Niamh Wynne; Giuliana Silvestri; Peter Humphries; Paul F Kenna; Matthew Carrigan; G Jane Farrar Journal: Genes (Basel) Date: 2017-11-03 Impact factor: 4.096