Gonzalvez M, Ho Wang Yin G, Gascon P, Denis D, Hoffart L
Aix-Marseille université, 13284 Marseille, France; Service d'ophtalmologie, hôpital de la Timone, AP-HM, 264, rue Saint-Pierre, 13385 Marseille, France.
Aix-Marseille université, 13284 Marseille, France; Service d'ophtalmologie, hôpital de la Timone, AP-HM, 264, rue Saint-Pierre, 13385 Marseille, France.
J Fr Ophtalmol. 2018 Dec;41(10):920-925. doi: 10.1016/j.jfo.2018.03.010. Epub 2018 Nov 13.
The objective of this article is to describe the evolution of Schnyder dystrophy in 3 related patients of different ages and to highlight the discovery of a new mutation unidentified until now.
We present a series of 3 cases, all first-degree relatives with no suggestion of consanguinity, of different ages (30, 40 and 59 years) and two distinct generations (mother and children). Slit lamp examination revealed the same lesions in our three patients: an early-onset corneal arcus senilis, central corneal deposits, and a gray stromal haze in the two oldest subjects. The older the patient, the more numerous and dense were these lesions. The various anterior segment OCTs showed an increase in the number of hyperreflective opacities in the anterior stroma and, in the older subject, the appearance of many posterior shadows. Monitoring of pachymetry by Pentacam showed progressive age-related thickening. All three patients had dyslipidemia treated with statins or diet alone. In our case we proposed treatment only to subject A because of the significant impact on her visual acuity.
Numerous clinical, para-clinical and genetic descriptions of this disease are found in the literature. Schnyder dystrophy is rare but not unheard of and may be discovered fortuitously or in the setting of decreased visual acuity. Genetic analysis of our family revealed a mutation of the UBIAD1 gene not described in the literature. UBIAD1 encodes the protein domain-containing UbiA prenyltransferase 1 which converts vitamin K1 into K2 and is involved in the cholesterol synthesis pathway. In the case of a mutation, it is no longer functional, leading to the accumulation of cholesterol crystals. Given the clinical context and the presence of this variant of the reference sequence in all relatives, its pathogenesis is strongly suspected in our family. The originality of our article is to present the progression of the same pathology in 3 patients with the same mutation at different ages and degrees of severity. This notion of progressive worsening and the need to treat late in the majority of cases are found in literature.
The discovery of a new variant within the UBAID1 gene suggests its pathogenesis in view of the clinical features available to us. The dystrophy is initially asymptomatic before the high number of deposits becomes disabling.
本文旨在描述3例不同年龄的相关患者中施奈德营养不良症的演变过程，并着重介绍迄今尚未发现的一种新突变。
我们呈现了3例病例，均为一级亲属，无血缘关系提示，年龄各异（30岁、40岁和59岁），分属两代（母亲和子女）。裂隙灯检查显示我们的3例患者有相同病变：早发性角膜老年环、角膜中央沉积物，以及年龄较大的两位患者出现的角膜基质灰色混浊。患者年龄越大，这些病变越多且越密集。各种眼前节光学相干断层扫描显示前基质中高反射混浊物数量增加，在年龄较大的患者中还出现许多后向阴影。Pentacam角膜测厚监测显示与年龄相关的渐进性增厚。所有3例患者均患有血脂异常，采用他汀类药物或单纯饮食治疗。在我们的病例中，仅对A患者进行了治疗，因为其对视力有显著影响。
文献中有关于该疾病的大量临床、辅助临床和遗传学描述。施奈德营养不良症较为罕见但并非闻所未闻，可能偶然发现或在视力下降时被发现。我们家族的基因分析发现了文献中未描述的UBIAD1基因突变。UBIAD1编码含蛋白结构域的泛醇基转移酶1，该酶将维生素K1转化为K2并参与胆固醇合成途径。发生突变时，它不再发挥功能，导致胆固醇晶体积累。鉴于临床情况以及所有亲属中均存在该参考序列变体，我们强烈怀疑其在我们家族中的发病机制。本文的独特之处在于呈现了3例具有相同突变、不同年龄和严重程度的患者中同一病理过程的进展情况。文献中也提到了这种进行性恶化的概念以及大多数情况下需要晚期治疗的必要性。
鉴于我们所掌握的临床特征，UBIAD1基因内新变体的发现提示了其发病机制。在大量沉积物导致功能障碍之前，营养不良症最初是无症状的。
