Section of Medical Genetics, Children's Specialist Hospital, King Fahad Medical City, Riyadh, Saudi Arabia.
Department of Pediatric Neurology, National Neuroscience Institute, King Fahad Medical City, Riyadh, Saudi Arabia.
Pediatr Neurol. 2024 Jun;155:149-155. doi: 10.1016/j.pediatrneurol.2024.03.004. Epub 2024 Mar 7.
Neuronal ceroid lipofuscinoses (NCLs) represent a heterogeneous group of inherited metabolic lysosomal disorders characterized by neurodegeneration. This study sought to describe the clinical and molecular characteristics of NCLs in Saudi Arabia and determine the most common types in that population.
A retrospective review of electronic medical records was conducted for 63 patients with NCL (55 families) from six tertiary and referral centers in Saudi Arabia between 2008 and 2022. Clinical, radiological, and neurophysiological data as well as genetic diagnoses were reviewed.
CLN6 was the predominant type, accounting for 45% of cases in 25 families. The most common initial symptoms were speech delay (53%), cognitive decline (50%) and/or gait abnormalities (48%), and seizure (40%). Behavioral symptomatology was observed in 20%, whereas visual impairment was less frequently (9.3%) encountered. Diffuse cerebral and cerebellar atrophy was the predominant finding on brain magnetic resonance imaging. Electroencephalography generally revealed background slowing in all patients with generalized epileptiform discharges in 60%. The most common genotype detected was the p.Ser265del variant found in 36% (20 of 55 families). The most rapidly progressive subtypes were CLN2 and CLN6. Two patients with each died at age five years. The earliest age at which a patient was nonambulatory was two years in a patient with CLN14.
This is the largest molecularly confirmed NCL cohort study from Saudi Arabia. Characterizing the natural history of specific NLC types can increase understanding of the underlying pathophysiology and distinctive genotype-phenotype characteristics, facilitating early diagnosis and treatment initiation as well as genetic counseling for families.
神经元蜡样脂褐质沉积症（NCLs）代表一组异质性的遗传性代谢性溶酶体疾病，其特征为神经退行性变。本研究旨在描述沙特阿拉伯的 NCL 临床和分子特征，并确定该人群中最常见的类型。
对 2008 年至 2022 年间沙特阿拉伯六家三级转诊中心的 63 名 NCL 患者（55 个家系）的电子病历进行了回顾性分析。回顾了临床、放射和神经生理学数据以及基因诊断。
CLN6 是主要类型，占 25 个家系中 45%的病例。最常见的首发症状是言语迟缓（53%）、认知能力下降（50%）和/或步态异常（48%）以及癫痫发作（40%）。20%的患者出现行为症状，而视力障碍则较少见（9.3%）。脑磁共振成像显示弥漫性脑和小脑萎缩。所有患者的脑电图均普遍显示背景减慢，其中 60%有广泛的癫痫样放电。最常见的基因型是 p.Ser265del 变异，占 36%（55 个家系中的 20 个）。进展最快的亚型是 CLN2 和 CLN6。两名患者均在五岁时死亡。CLN14 患者中最早不能行走的年龄是两岁。
这是沙特阿拉伯最大的分子确诊 NCL 队列研究。描述特定 NLC 类型的自然病史可以提高对潜在病理生理学和独特基因型-表型特征的认识，从而促进早期诊断和治疗开始以及为家庭提供遗传咨询。
