Neurodevelopmental and Behavioral Phenotyping Service, National Institute of Mental Health, NIH, DHHS, Bethesda, MD.
National Human Genome Research Institute, National Institute of Mental Health, NIH, DHHS, Bethesda, MD.
J Dev Behav Pediatr. 2020 Jun/Jul;41(5):388-396. doi: 10.1097/DBP.0000000000000785.
Niemann-Pick disease type C1 (NPC1) is a lysosomal storage disease characterized by progressive neurodegeneration, with the age of diagnosis ranging from the prenatal period through adulthood. Although neurological symptoms usually precede genetic diagnosis, they do not necessarily prompt diagnosis in the early years. Few prospective data are available to describe neurological onset, including neurodevelopmental delays, in children with NPC1. This dearth of information hinders the planning and implementation of adequate monitoring and treatment for the neurodevelopmental sequelae of NPC1.
Twenty-nine infants, toddlers, and preschoolers younger than 6 years participated in a natural history study and were administered neurodevelopmental assessments using instruments commonly used for early intervention screening in the community.
Twenty-two of 29 participants met the criteria for a significant delay of at least 1.5 SDs below the mean in at least one domain of development; the youngest children often met these criteria for a significant delay based on motor delays, but cognitive and language delays were also common. However, only 11 of the 22 participants were reported to receive early intervention services before study entry.
Although neurological symptoms may not prompt the genetic diagnosis of NPC1, the current findings support the use of a multimethod approach to repeated assessments for young children with the diagnosis because of the frequency of developmental delays or decline in multiple domains. The diagnosis of NPC1 alone should qualify children for evaluation for early intervention services and consideration of investigational therapeutic interventions.
尼曼-匹克病 C1 型（NPC1）是一种溶酶体贮积病，其特征为进行性神经退行性变，诊断年龄从产前到成年期不等。尽管神经症状通常先于基因诊断，但它们并不一定会促使早期诊断。目前几乎没有关于 NPC1 患儿神经发作（包括神经发育迟缓）的前瞻性数据。缺乏这些信息会妨碍为 NPC1 的神经发育后遗症规划和实施充分的监测和治疗。
29 名年龄小于 6 岁的婴儿、幼儿和学龄前儿童参加了一项自然史研究，并使用社区中常用于早期干预筛查的工具进行了神经发育评估。
29 名参与者中有 22 名至少在一个发育领域的发育迟缓达到均值的 1.5 个标准差以上，被认为存在显著发育迟缓；最小的孩子通常根据运动迟缓达到这些标准，但认知和语言迟缓也很常见。然而，在研究入组前，只有 11 名符合条件的参与者被报告接受了早期干预服务。
尽管神经症状可能不会提示 NPC1 的基因诊断，但目前的研究结果支持对诊断为 NPC1 的幼儿采用多方法重复评估，因为这些孩子在多个领域存在发育迟缓或发育下降的频率较高。仅 NPC1 的诊断就应使儿童有资格接受早期干预服务的评估，并考虑进行试验性治疗干预。
