PDF(Pubmed)
Abstract：
We present here the case histories of two siblings, a boy and a girl, with Leber\'s congenital amaurosis (LCA). The diagnosis was based on non-recordable full-field electroretinogram (ffERG). The long-term ophthalmologic follow-up included kinetic perimetry (Goldmann), visual evoked potentials with flash stimulation, optical coherence tomography (OCT: B-scan images at the area of fovea), and multifocal ERG. The boy (sibling 1, born in 1986) was sent for electrophysiological examination at the age of four because he had nystagmus from birth. The diagnosis would be LCA based on non-recordable ffERG. Four years later, his visual acuity decreased rapidly due to vitreous opacification, caused by the autoimmune reaction of the retinal pigment epithelial cells. This was treated successfully with steroid injections, administered parabulbarly. Retinal autoimmune panel was not performed. Genetic testing became available only in 2019, and it revealed a RPE65 gene mutation: (NM_000329.2) c.{442G>A};{442G>A} (p.{Glu148Lys}; {Glu148Lys}). His sister (sibling 2, born in 1993) showed similar symptoms, caused by the same genetic mutation. Even though their parents were free of symptoms, it appeared that they were heterozygous carriers of the same mutation. Research of the family tree revealed a consanguineous marriage four generations before. Both siblings received successful gene therapy relatively late in their age: sibling 1 was 35 and sibling 2 was 28 years old, meaning that they were at an advanced stage of the disease. Nevertheless, follow-up examinations showed measurable improvements in their retinal function. The study shows that electrophysiological examinations, including flash-evoked responses, are useful in the objective evaluation of the progression in the central photoreceptor loss during the follow-up of LCA. The results also show that gene therapy can have beneficial effects even at an advanced stage of the disease.
摘要：
我们在这里介绍两个兄弟姐妹的病史，一个男孩和一个女孩,患有Leber先天性黑蒙（LCA）。诊断基于不可记录的全场视网膜电图（ffERG）。长期眼科随访包括动力学视野检查（Goldmann），视觉诱发电位与闪光刺激，光学相干断层扫描（OCT：中央凹区域的B扫描图像），和多病灶ERG。这个男孩（兄弟姐妹1，1986年出生）在四岁时被送去进行电生理检查，因为他从出生就有眼球震颤。诊断将是基于不可记录的ffERG的LCA。四年后,由于玻璃体混浊，他的视力迅速下降，由视网膜色素上皮细胞的自身免疫反应引起。这是通过类固醇注射成功治疗的，扑通管理。未进行视网膜自身免疫组。基因检测仅在2019年开始使用，它揭示了RPE65基因突变：（NM_000329.2）c。{442G>A}；{442G>A}（p。{Glu148Lys};{Glu148Lys})。他的妹妹（兄弟姐妹2，1993年出生）表现出类似的症状，由相同的基因突变引起的。即使他们的父母没有症状，它们似乎是相同突变的杂合携带者。对家谱的研究揭示了四代人之前的近亲婚姻。两个兄弟姐妹都在年龄相对较晚的时候接受了成功的基因治疗：兄弟姐妹1是35岁，兄弟姐妹2是28岁，这意味着他们处于疾病的晚期。然而，随访检查显示其视网膜功能有显著改善.研究表明，电生理检查，包括闪光诱发的反应，可用于客观评估LCA随访期间中央光感受器损失的进展。结果还表明，即使在疾病的晚期阶段，基因疗法也可以产生有益的效果。
