Guelbert Norberto, Espitia Segura Oscar Mauricio, Amoretti Carolina, Arteaga Arteaga Angélica, Atanacio Nora Graciela, Bazan Natacha Sabrina, Carvalho Ellaine Doris Fernandes, Carvalho de Andrade Maria Denise Fernandes, Denzler Inés María, Durand Consuelo, Ribeiro Erlane, Giugni Juan Carlos, González Gabriel, González Moron Dolores, Guelbert Guillermo, Hernández Rodriguez Zulma Janneth, Embiruçu Emilia Katiane, Kauffman Marcelo Andrés, Mancilla Nury Isabel, Marcon Laureano, Marques Pereira Alessandra, Fischinger Moura de Souza Carolina, Muñoz Victor Adrián, Naranjo Flórez Ricardo Andrés, Pessoa André Luiz, Ruiz María Victoria, Solano Villareal Martha Luz, Spécola Norma, Tavera Lina Marcela, Tello Javiera, Troncoso Schifferli Mónica, Ugrina Sonia, Vaccarezza María Magdalena, Vergara Diane, Villanueva María Mercedes
Clínica Universitaria Reina Fabiola, Córdoba, Argentina.
Fundación Hospital Pediátrico la Misericordia, Bogotá, Colombia.
Mol Genet Metab Rep. 2024 Feb 1;38:101060. doi: 10.1016/j.ymgmr.2024.101060. eCollection 2024 Mar.
Late infantile neuronal ceroid lipofuscinosis type 2 (CLN2), is a neurodegenerative autosomal recessive disease caused by gene variants with a spectrum of classic and atypical phenotypes. The aim of treatment is to slow functional decline as early as possible in an attempt to improve quality of life and survival. This study describes the clinical characteristics as well as the response to treatment with cerliponase alfa.
A retrospective study was conducted in five Latin-American countries, using clinical records from patients with CLN2. Clinical follow-up and treatment variables are described. A descriptive and bivariate statistical analysis was performed.
A total of 36 patients were observed (range of follow-up of 61-110 weeks post-treatment). At presentation, patients with the classic phenotype ( = 16) exhibited regression in language (90%), while seizures were the predominant symptom (87%) in patients with the atypical phenotype ( = 20). Median age of symptom onset and time to first specialized consultation was 3 (classical) and 7 (atypical) years, while the median time interval between onset of symptoms and treatment initiation was 4 years (classical) and 7.5 (atypical). The most frequent variant was c.827 A > T in 17/72 alleles, followed by c.622C > T in 6/72 alleles. All patients were treated with cerliponase alfa, and either remained functionally stable or had a loss of 1 point on the CLN2 scale, or up to 2 points on the Wells Cornel and Hamburg scales, when compared to pretreatment values.
This study reports the largest number of patients with CLN2 currently on treatment with cerliponase alfa in the world. Data show a higher frequency of patients with atypical phenotypes and a high allelic proportion of intron variants in our region. There was evidence of long intervals until first specialized consultation, diagnosis, and enzyme replacement therapy. Follow-up after the initiation of cerliponase alfa showed slower progression or stabilization of the disease, associated with adequate clinical outcomes and stable functional scores. These improvements were consistent in both clinical phenotypes.
2型晚发性婴儿神经元蜡样脂褐质沉积症（CLN2）是一种神经退行性常染色体隐性疾病，由基因变异引起，具有一系列典型和非典型表型。治疗的目的是尽早减缓功能衰退，以提高生活质量和延长生存期。本研究描述了CLN2患者的临床特征以及对阿法西普酶治疗的反应。
在五个拉丁美洲国家进行了一项回顾性研究，使用CLN2患者的临床记录。描述了临床随访和治疗变量。进行了描述性和双变量统计分析。
共观察了36例患者（治疗后随访时间为61 - 110周）。就诊时，典型表型患者（n = 16）语言功能衰退的发生率为90%，而非典型表型患者（n = 20）癫痫发作是主要症状（87%）。症状出现的中位年龄和首次专科会诊时间，典型表型患者为3岁，非典型表型患者为7岁，而症状出现至开始治疗的中位时间间隔，典型表型患者为4年，非典型表型患者为7.5年。最常见的变异是17/72个等位基因中的c.827A>T，其次是6/72个等位基因中的c.622C>T。所有患者均接受阿法西普酶治疗，与治疗前值相比，功能要么保持稳定，要么在CLN2量表上下降1分，在韦尔斯康奈尔量表和汉堡量表上最多下降2分。
本研究报告了目前世界上接受阿法西普酶治疗的CLN2患者数量最多。数据显示，我们地区非典型表型患者的频率较高，内含子变异的等位基因比例较高。有证据表明，首次专科会诊、诊断和酶替代治疗的间隔时间较长。开始使用阿法西普酶治疗后的随访显示，疾病进展较慢或稳定，临床结果良好，功能评分稳定。两种临床表型的改善情况均一致。
