Morison Lottie D, Whiteman Ineka T, Vogel Adam P, Tilbrook Lisa, Fahey Michael C, Braden Ruth, Bredebusch Joanna, Hildebrand Michael S, Scheffer Ingrid E, Morgan Angela T
Speech and Language, Murdoch Children's Research Institute, Parkville, Victoria, Australia.
Department of Audiology and Speech Pathology, The University of Melbourne, Parkville, Victoria, Australia.
J Inherit Metab Dis. 2025 Jan;48(1):e12838. doi: 10.1002/jimd.12838.
CLN2 and CLN3 diseases, the most common types of Batten disease (also known as neuronal ceroid lipofuscinosis), are childhood dementias associated with progressive loss of speech, language and feeding skills. Here we delineate speech, language, non-verbal communication and feeding phenotypes in 33 individuals (19 females) with a median age of 9.5 years (range 3-28 years); 16 had CLN2 and 17 CLN3 disease; 8/15 (53%) participants with CLN2 and 8/17 (47%) participants with CLN3 disease had speech and language impairments prior to genetic diagnosis. At the time of study all participants, bar one, had language impairments. The remaining participant with typical language was tested at age 3 years, following pre-symptomatic enzyme replacement therapy (ERT) from age 9 months. CLN2 and CLN3 disease had different profiles. For CLN2 disease, all affected individuals showed language impairment with dysarthria; older individuals with classical disease progressively became non-verbal. For CLN3 disease, the presentation was more heterogeneous. Speech impairment was evident early in the disease course, with dysarthria (13/15, 87%), often manifesting as neurogenic stuttering (5/15, 33%). Participants with CLN2 disease had comparable expressive and receptive language skills (p > 0.99), yet participants with CLN3 disease had stronger expressive language than receptive language skills (p = 0.004). Speech, cognitive and language impairment and adaptive behaviour showed progressive decline in both diseases. Individuals with pre-symptomatic ERT or atypical CLN2 disease were less impaired. Challenging behaviours were common in CLN3 (11/17, 65%), but less frequent in CLN2 (4/16, 25%) disease. Individuals with Batten disease require tailored speech therapy incorporating communication partner training utilising environment adaptations and informal communication behaviours.
CLN2和CLN3疾病是贝敦氏病（也称为神经元蜡样脂褐质沉积症）最常见的类型，是与言语、语言和进食技能逐渐丧失相关的儿童期痴呆症。在此，我们描述了33名个体（19名女性）的言语、语言、非言语交流和进食表型，这些个体的中位年龄为9.5岁（范围3 - 28岁）；其中16人患有CLN2疾病，17人患有CLN3疾病；15名CLN2疾病参与者中有8名（53%）和17名CLN3疾病参与者中有8名（47%）在基因诊断之前存在言语和语言障碍。在研究时，除一人外，所有参与者都有语言障碍。其余一名语言正常的参与者在9个月开始进行症状前酶替代疗法（ERT）后，3岁时接受了测试。CLN2和CLN3疾病具有不同的特征。对于CLN2疾病，所有受影响个体均表现出伴有构音障碍的语言障碍；患有典型疾病的年长个体逐渐变得无法言语。对于CLN3疾病，表现更为多样。言语障碍在疾病病程早期就很明显，存在构音障碍（15人中的13人，87%），常表现为神经性口吃（15人中的5人，33%）。CLN2疾病参与者的表达性和接受性语言技能相当（p > 0.99），而CLN3疾病参与者的表达性语言技能强于接受性语言技能（p = 0.004）。言语、认知和语言障碍以及适应性行为在两种疾病中均呈逐渐下降趋势。接受症状前ERT或非典型CLN2疾病的个体受损较轻。挑战性行为在CLN3疾病中很常见（17人中的11人，65%），但在CLN2疾病中较少见（16人中的4人，25%）。患有贝敦氏病的个体需要量身定制的言语治疗，包括利用环境适应和非正式交流行为进行交流伙伴训练。
