Guelbert Guillermo, Venier Ana Clara, Cismondi Ines Adriana, Becerra Adriana, Vazquez Juan Carlos, Fernández Elmer Andrés, De Paul Ana Lucía, Guelbert Norberto, Noher Ines, Pesaola Favio
Programa de Investigación Translacional de Lipofuscinosis Ceroidea Neuronal (NCL Program), Hospital de Niños de la Santísima Trinidad, Córdoba, Argentina.
Servicio de Enfermedades Metabólicas Hereditarias, Hospital de Niños de la Santísima Trinidad, Córdoba, Argentina.
Front Neurol. 2022 Aug 12;13:920421. doi: 10.3389/fneur.2022.920421. eCollection 2022.
Neuronal ceroid lipofuscinoses (NCLs) comprise 13 hereditary neurodegenerative pathologies of very low frequency that affect individuals of all ages around the world. All NCLs share a set of symptoms that are similar to other diseases. The exhaustive collection of data from diverse sources (clinical, genetic, neurology, ophthalmology, etc.) would allow being able in the future to define this group with greater precision for a more efficient diagnostic and therapeutic approach. Despite the large amount of information worldwide, a detailed study of the characteristics of the NCLs in South America and the Caribbean region (SA&C) has not yet been done. Here, we aim to present and analyse the multidisciplinary evidence from all the SA&C with qualitative weighting and biostatistical evaluation of the casuistry. Seventy-one publications from seven countries were reviewed, and data from 261 individuals (including 44 individuals from the Cordoba cohort) were collected. Each NCL disease, as well as phenotypical and genetic data were described and discussed in the whole group. The CLN2, CLN6, and CLN3 disorders are the most frequent in the region. Eighty-seven percent of the individuals were 10 years old or less at the onset of symptoms. Seizures were the most common symptom, both at onset (51%) and throughout the disease course, followed by language (16%), motor (15%), and visual impairments (11%). Although symptoms were similar in all NCLs, some chronological differences could be observed. Sixty DNA variants were described, ranging from single nucleotide variants to large chromosomal deletions. The diagnostic odyssey was probably substantially decreased after medical education activities promoted by the pharmaceutical industry and parent organizations in some SA&C countries. There is a statistical deviation in the data probably due to the approval of the enzyme replacement therapy for CLN2 disease, which has led to a greater interest among the medical community for the early description of this pathology. As a general conclusion, it became clear in this work that the combined bibliographical/retrospective evaluation approach allowed a general overview of the multidisciplinary components and the epidemiological tendencies of NCLs in the SA&C region.
神经元蜡样脂褐质沉积症（NCLs）包括13种非常罕见的遗传性神经退行性疾病，影响着世界各地所有年龄段的个体。所有NCLs都有一组与其他疾病相似的症状。从不同来源（临床、遗传、神经学、眼科等）详尽收集数据，将有助于未来更精确地界定这一疾病群体，从而采取更有效的诊断和治疗方法。尽管全球已有大量信息，但南美洲和加勒比地区（SA&C）NCLs特征的详细研究尚未开展。在此，我们旨在呈现并分析来自整个SA&C地区的多学科证据，并对病例进行定性加权和生物统计学评估。我们查阅了来自七个国家的71篇出版物，并收集了261名个体的数据（包括科尔多瓦队列中的44名个体）。对整个群体中的每种NCL疾病以及表型和遗传数据进行了描述和讨论。CLN2、CLN6和CLN3疾病在该地区最为常见。87%的个体在症状出现时年龄在10岁及以下。癫痫是最常见的症状，在发病时（51%）以及整个病程中都是如此，其次是语言障碍（16%）、运动障碍（15%）和视力障碍（11%）。尽管所有NCLs的症状相似，但仍可观察到一些时间上的差异。共描述了60种DNA变异，范围从单核苷酸变异到大型染色体缺失。在一些SA&C国家，制药行业和家长组织开展医学教育活动后，诊断过程可能大幅缩短。数据存在统计偏差，可能是由于CLN2疾病的酶替代疗法获批，这使得医学界对该疾病的早期描述更感兴趣。总的来说，在这项工作中很明显，文献/回顾性综合评估方法能够对SA&C地区NCLs的多学科组成部分和流行病学趋势有一个总体了解。
