Gyrate atrophy of the choroid and retina (GACR) is a rare inborn error of amino acid metabolism caused by bi-allelic variations in OAT. GACR is characterised by vision decline in early life eventually leading to complete blindness, and high plasma ornithine levels. There is no curative treatment for GACR, although several therapeutic modalities aim to slow progression of the disease by targeting different steps within the ornithine pathway. No international treatment protocol is available. We systematically collected all international literature on therapeutic interventions in GACR to provide an overview of published treatment effects.

Methods

Following the PRISMA guidelines, we conducted a systematic review of the English literature until December 22nd 2020. PubMed and Embase databases were searched for studies related to therapeutic interventions in patients with GACR.

Results

A total of 33 studies (n = 107 patients) met the inclusion criteria. Most studies were designed as case reports (n = 27) or case series (n = 4). No randomised controlled trials or large cohort studies were found. Treatments applied were protein-restricted diets, pyridoxine supplementation, creatine or creatine precursor supplementation, l-lysine supplementation, and proline supplementation. Protein-restricted diets lowered ornithine levels ranging from 16.0–91.2%. Pyridoxine responsiveness was reported in 30% of included mutations. Lysine supplementation decreased ornithine levels with 21–34%. Quality assessment showed low to moderate quality of the articles.

Conclusions

Based primarily on case reports ornithine levels can be reduced by using a protein restricted diet, pyridoxine supplementation (variation-dependent) and/or lysine supplementation. The lack of pre-defined clinical outcome measures and structural follow-up in all included studies impeded conclusions on clinical effectiveness. Future research should be aimed at 1) Unravelling the OAT biochemical pathway to identify other possible pathologic metabolites besides ornithine, 2) Pre-defining GACR specific clinical outcome measures, and 3) Establishing an international historical cohort.

中文翻译：

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脉络膜和视网膜回旋萎缩（GACR）的治疗方法综述

脉络膜和视网膜旋转性萎缩（GACR）是一种罕见的先天性氨基酸代谢错误，由OAT的双等位基因变异引起。GACR 的特点是生命早期视力下降，最终导致完全失明和血浆鸟氨酸水平升高。GACR 没有治愈性治疗方法，尽管几种治疗方式旨在通过针对鸟氨酸途径中的不同步骤来减缓疾病的进展。没有国际治疗方案可用。我们系统地收集了所有关于 GACR 治疗干预的国际文献，以概述已发表的治疗效果。

方法

根据 PRISMA 指南，我们对英文文献进行了系统回顾，直至 2020 年 12 月 22 日。在 PubMed 和 Embase 数据库中搜索了与 GACR 患者的治疗干预相关的研究。

结果

共有 33 项研究（n = 107 名患者）符合纳入标准。大多数研究被设计为病例报告（n = 27）或病例系列（n = 4）。没有发现随机对照试验或大型队列研究。应用的治疗是蛋白质限制饮食、吡哆醇补充、肌酸或肌酸前体补充、l-赖氨酸补充和脯氨酸补充。限制蛋白质的饮食将鸟氨酸水平降低了 16.0-91.2%。在 30% 的包含突变中报告了吡哆醇反应性。赖氨酸补充剂降低了 21-34% 的鸟氨酸水平。质量评估显示文章质量低到中等。

结论

主要基于病例报告，可以通过使用限制蛋白质的饮食、补充吡哆醇（依赖于变化）和/或补充赖氨酸来降低鸟氨酸水平。在所有纳入的研究中缺乏预先定义的临床结果测量和结构性随访阻碍了关于临床有效性的结论。未来的研究应针对 1) 解开 OAT 生化途径以识别除鸟氨酸之外的其他可能的病理代谢物，2) 预先定义 GACR 特定的临床结果测量，以及 3) 建立国际历史队列。