Background

Neuronal ceroid lipofuscinoses (NCLs) (hereafter described as CLN disease) comprise a rare and life-limiting set of genetically inherited neurodegenerative disorders that are characterized by abnormal lysosomal storage. The NCL disorders are, collectively, the most common group of degenerative brain disorders in children.

Patient Descriptions

We report two cases of CLN disease that were diagnosed and treated at the Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand. Both cases of CLN disease (CLN1 and CLN6 diagnosed in 2016 and 2017, respectively) profiled in this report presented with clinical features of Rett syndrome. In the first case, a 2-year-old girl presented with Rett-like clinical features, including global developmental regression and hand-wringing action. Single-gene analysis of the MECP2 gene was negative. However, PPT1 gene sequencing revealed a novel homozygous frameshift mutation, c.629_630dupGT (p.Ile211Valfs∗10). In the second case, a 7.5-year-old girl presented with ataxia, progressive myoclonic epilepsy, and Rett-like hand-wringing. A c.794_796delCCT variant in the CLN6 gene was identified by whole-exome sequencing. Fingerprint bodies from electron microscopy of the skin also supported a diagnosis of CLN disease in our second case.

Discussion

Presentation with clinical features of Rett syndrome has only been reported in patients diagnosed with CLN1 and CLN7 disease, and never in those with CLN6.

Conclusions

Physicians should suspect and investigate for CLN disease in patients with Rett-like phenotype who are negative for MECP2 mutation, especially in patients with visual impairment and early prominent brain atrophy.

中文翻译：

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呈现为 Rett 样表型的神经元蜡样脂褐质：来自泰国的两例报告

背景

神经元蜡样脂褐质沉积症 (NCL)（以下称为 CLN 病）包括一组罕见的、限制生命的遗传性神经退行性疾病，其特征是溶酶体贮积异常。NCL 疾病是儿童中最常见的一组退行性脑疾病。

患者描述

我们报告了两例在泰国曼谷玛希隆大学 Siriraj 医学院儿科诊断和治疗的 CLN 疾病病例。本报告中描述的两例 CLN 疾病（分别于 2016 年和 2017 年诊断出的 CLN1 和 CLN6）均呈现出 Rett 综合征的临床特征。在第一个案例中，一名 2 岁女孩出现了类似 Rett 的临床特征，包括整体发育倒退和绞手动作。MECP2基因的单基因分析是阴性的。然而，PPT1基因测序揭示了一种新的纯合移码突变，c.629_630dupGT (p.Ile211Valfs∗10)。在第二个病例中，一名 7.5 岁女孩出现共济失调、进行性肌阵挛性癫痫和 Rett 样手绞痛。通过全外显子组测序鉴定了CLN6基因中的 c.794_796delCCT 变体。在我们的第二个病例中，来自皮肤电子显微镜的指纹体也支持 CLN 疾病的诊断。

讨论

仅在诊断为 CLN1 和 CLN7 疾病的患者中报告了具有 Rett 综合征临床特征的表现，而从未在 CLN6 患者中报告过。

结论

对于MECP2突变阴性的 Rett 样表型患者，尤其是视力障碍和早期明显脑萎缩的患者，医生应怀疑和调查 CLN 疾病。