尼曼-皮克病 C1 型的听觉表型。
Auditory phenotype of Niemann-Pick disease, type C1.
机构信息
1Department of Health and Human Services, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD; 2Department of Hearing and Speech Sciences, University of Maryland College Park, College Park, MD; 3Department of Health and Human Services, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD; 4Department of Human Development and Quantitative Methodology, University of Maryland College Park, College Park, MD.
出版信息
Ear Hear. 2014 Jan-Feb;35(1):110-7. doi: 10.1097/AUD.0b013e3182a362b8.
OBJECTIVES
The aim of this study was to comprehensively evaluate the auditory phenotype in Niemann-Pick disease, type C1 (NPC1), to understand better the natural history of this complex, heterogeneous disorder, and to define further the baseline auditory deficits associated with NPC1 so that use of potentially ototoxic interventions (e.g., 2-hydroxypropyl-ß-cyclodextrin) may be more appropriately monitored and understood.
DESIGN
Fifty patients with NPC1 ranging in age from 4 months to 21 years (mean = 9.3 years) enrolled in a natural history/observational study at the National Institutes of Health. The auditory test battery included, when possible, immittance audiometry, pure-tone and speech audiometry, otoacoustic emission testing, and a neurotologic auditory brainstem response study. Longitudinal data were collected on a subset of patients.
RESULTS
Over half of the cohort exhibited hearing loss involving the high frequencies ranging from a slight to moderate degree, and 74% of patients presented with clinically significant hearing loss involving the frequencies most important to speech understanding (0.5, 1, 2, 4 kHz). Despite the heterogeneity of the sample, results among patients were sufficiently consistent to implicate retrocochlear dysfunction in the majority (66%) of individuals, with (22%) or without (44%) accompanying cochlear involvement. Some patients (10%) presented with a profile for auditory neuropathy spectrum disorder. The combination of cross-sectional and longitudinal data indicates these patients are at risk for a progressive decline in auditory function.
CONCLUSIONS
This is the largest cohort of patients with NPC1 evaluated comprehensively for auditory dysfunction, and results implicate the pathological processes of NPC1 in the manifestation of hearing loss. Patients with NPC1 should be monitored audiologically throughout their lives, beginning at the time of diagnosis. Clinicians and researchers should be aware of this historically overlooked aspect of the phenotype.
目的
本研究旨在全面评估尼曼-皮克病 C1 型（NPC1）的听觉表型，以更好地了解这种复杂、异质性疾病的自然史，并进一步确定与 NPC1 相关的基线听觉缺陷，以便更适当地监测和理解可能具有耳毒性的干预措施（例如 2-羟丙基-β-环糊精）的使用。
设计
50 名 NPC1 患者，年龄从 4 个月到 21 岁（平均 9.3 岁），参加了美国国立卫生研究院的一项自然史/观察性研究。听觉测试包括在可能的情况下进行中耳导抗测试、纯音和言语测听、耳声发射测试和神经听觉脑干反应研究。对一部分患者进行了纵向数据收集。
结果
超过一半的队列表现出高频听力损失，程度从轻度到中度不等，74%的患者表现出与言语理解最重要的频率（0.5、1、2、4 kHz）相关的临床显著听力损失。尽管样本存在异质性，但患者之间的结果足够一致，表明大多数（66%）个体存在耳蜗后功能障碍，伴有（22%）或不伴有（44%）耳蜗受累。一些患者（10%）表现出听觉神经病谱障碍的特征。横断面和纵向数据的结合表明这些患者有听觉功能进行性下降的风险。
结论
这是迄今为止对 NPC1 患者进行听觉功能障碍全面评估的最大队列，结果表明 NPC1 的病理过程导致了听力损失的发生。NPC1 患者应在其一生中进行听觉监测，从诊断时开始。临床医生和研究人员应该意识到表型中这一被忽视的历史方面。
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