Lourenço Charles M, Pessoa Andre, Mendes Carmen C, Rivera-Nieto Carolina, Vergara Diane, Troncoso Mónica, Gardner Emily, Mallorens Francisca, Tavera Lina, Lizcano Luis A, Atanacio Nora, Guelbert Norberto, Specola Norma, Mancilla Nury, de Souza Carolina F M, Mole Sara E
School of Medicine, Estácio University Center, Ribeirão Preto, São Paulo, Brazil.
Pediatric Neurology Service, Albert Sabin Children's Hospital, University of Ceará State, Fortaleza, Ceará, Brazil.
J Paediatr Child Health. 2021 Apr;57(4):519-525. doi: 10.1111/jpc.15250. Epub 2020 Dec 30.
Neuronal ceroid lipofuscinosis type 2 (CLN2) disease is an autosomal recessive inherited neurodegenerative lysosomal storage disorder caused by deficient tripeptidyl peptidase 1 (TPP1) enzyme, leading to progressive deterioration of neurological functions commonly occurring in children aged 2-4 years and culminating in early death. Atypical cases associated with earlier or later symptom onset, or even protracted course, have already been reported. Such variable manifestations may constitute an additional challenge to early diagnosis and initiation of appropriate treatment. The present work aimed to analyse clinical data from a cohort of Latin American CLN2 patients with atypical phenotypes.
Experts in inborn errors of metabolism from Latin America selected patients from their centres who were deemed by the clinicians to have atypical forms of CLN2, according to the current literature on this topic and their practical experience. Clinical and genetic data from the medical records were retrospectively revised. All cases were presented and analysed by these experts at an Advisory Board Meeting in São Paulo, Brazil, in October 2018.
Seizures, language abnormalities and behavioural disorders were found as the first manifestations, appearing at the median age of 6 years, an older age than classically described for the late infantile form. Three novel mutations were also identified.
Our findings reinforce the inclusion of CLN2 in the differential diagnosis of children presenting with seizures, behavioural disorders and language abnormalities. Early diagnosis will allow early initiation of specific therapy.
2型神经元蜡样脂褐质沉积症（CLN2）是一种常染色体隐性遗传的神经退行性溶酶体贮积症，由三肽基肽酶1（TPP1）酶缺乏引起，导致神经功能进行性恶化，常见于2至4岁儿童，最终导致早亡。已经报道了与症状出现较早或较晚，甚至病程迁延相关的非典型病例。这种表现的多样性可能给早期诊断和开始适当治疗带来额外挑战。本研究旨在分析一组具有非典型表型的拉丁美洲CLN2患者的临床资料。
拉丁美洲先天性代谢缺陷方面的专家根据关于该主题的当前文献及其实践经验，从各自中心挑选出临床医生认为患有非典型CLN2形式的患者。对病历中的临床和基因数据进行回顾性修订。所有病例在2018年10月于巴西圣保罗举行的咨询委员会会议上由这些专家进行展示和分析。
癫痫发作、语言异常和行为障碍被发现为首发表现，出现的中位年龄为6岁，比经典描述的晚婴儿型发病年龄要大。还鉴定出三个新的突变。
我们的研究结果强化了在对出现癫痫发作、行为障碍和语言异常的儿童进行鉴别诊断时将CLN2纳入考虑。早期诊断将有助于尽早开始特异性治疗。
