Heller Dan, Weiner Chen, Nasie Iris, Anikster Yair, Landau Yuval, Koren Tal, Pokroy Russell, Abulafia Adi, Pras Eran
a Ophthalmology Department , Assaf Harofeh Medical Center , Zerifin , Israel.
b Matlow's Ophthalmogenetic Laboratory, Assaf Harofeh Medical Center , Zerifin , Israel.
Ophthalmic Genet. 2017 Dec;38(6):549-554. doi: 10.1080/13816810.2017.1301966. Epub 2017 Apr 7.
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.
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.
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).
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.
本研究报告了两个患有回旋状萎缩（GA）的家系。本研究的目的是描述治疗方案对黄斑水肿的潜在影响。
对两名无关的GA患者进行研究，观察低蛋白饮食（≤0.8克/千克/天）和口服吡哆醇（500毫克/天）对血清鸟氨酸水平、最佳矫正视力（BCVA）、裂隙灯检查、光学相干断层扫描（OCT）和自发荧光检查结果的潜在影响。对用于OAT基因DNA、mRNA和外显子的血样进行相关突变和剪接效应筛查。
就诊时，两名患者均表现出GA的典型眼科特征，包括黄斑囊样水肿（CME）。一名患者还表现出视神经乳头错构瘤。治疗后，所有四只研究眼的鸟氨酸水平降低，BCVA改善，黄斑中心厚度（CMT）明显下降。分子病理特征包括一个新的剪接位点突变（c.900+1G>A）。
我们在GA患者中鉴定出一个新突变和两个先前描述的突变。其中，一名患者表现出不寻常的表型，包括双侧星形细胞错构瘤。我们首次认识到低蛋白摄入和补充吡哆醇治疗后CME有所改善。这一发现可能对理解黄斑水肿的治疗选择具有重要意义，无论其潜在病因如何。
