Introduction

Neuronal ceroid lipofuscinoses (CLN) are neurodegenerative disorders among the most frequent, inherited as an autosomal recessive trait. Affected patients can present with progressive decline in cognitive and motor functions, seizures, a shortened life span and visual deficiency. CLN2 is one of the rare CLN that benefits from treatment by cerliponase alpha an enzyme replacement therapy. Preliminary results on treated animal models have shown delayed neurological signs and prolonged life span. However, cerliponase alpha did not prevent vision loss or retinal degeneration in those animal models. Cerliponase alpha has currently been delivered to a few CLN2-affected patients. We report the case of one patient suffering from CLN2 treated with intracerebroventricular infusions of cerliponase alpha 300 mg every two weeks. Evolution of his retinal function was assessed by three successive flash-ERG and flash-VEP recordings throughout his treatment over a 4-year period.

Results

Before treatment at the age of 4 years 5 months, patient’s retinas were normal (normal fundi and normal flash-ERG). After 29 infusions at the age of 6 years 10 months, a-wave combined response was absent, while cone and flicker responses were normal. After 80 infusions at the age of 8 years 9 months, a-wave cone response was absent with b-wave peak time increased, and no combined response.

Comments

Despite treatment, our patient’s retinas showed a progressive abnormal and inhomogeneous function. Rods function was altered first, then the scotopic system and afterward, the cones. This result differs from those recorded in animal models. The relative preservation of cone functioning for a while could not be unequivocally attributed to enzyme replacement therapy as we lack comparison with the evolution of flash-ERGs recorded in untreated subjects.

中文翻译：

---

用 cerliponase alpha 治疗一名患有神经元蜡样脂褐质沉着症 CLN2 的儿童通过 flash-ERG 对视网膜功能的演变：病例报告

介绍

神经元蜡样脂褐质沉积症 (CLN) 是最常见的神经退行性疾病，作为常染色体隐性遗传。受影响的患者可能会出现认知和运动功能进行性下降、癫痫发作、寿命缩短和视力缺陷。CLN2 是一种罕见的 CLN，它受益于 cerliponase alpha 一种酶替代疗法的治疗。治疗动物模型的初步结果显示神经系统症状延迟和寿命延长。然而，cerliponase alpha 并不能防止这些动物模型中的视力丧失或视网膜变性。Cerliponase alpha 目前已交付给一些受 CLN2 影响的患者。我们报告了一名患有 CLN2 的患者每两周接受脑室内注射 cerliponase alpha 300 mg 治疗的病例。

结果

在 4 岁 5 个月大的治疗前，患者的视网膜正常（正常的眼底和正常的 flash-ERG）。在 6 岁 10 个月时输注 29 次后，a 波联合反应消失，而锥形和闪烁反应正常。在 8 岁 9 个月时输注 80 次后，a 波锥体反应消失，b 波峰值时间增加，无联合反应。

注释

尽管进行了治疗，但我们患者的视网膜显示出进行性异常和不均匀的功能。首先改变视杆功能，然后是暗视系统，然后是视锥细胞。该结果与动物模型中记录的结果不同。一段时间内锥体功能的相对保存不能明确归因于酶替代疗法，因为我们缺乏与未治疗受试者中记录的 flash-ERG 进化的比较。