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Auditory Phenotype of Niemann-Pick Disease, Type C1

King, Kelly A.1; Gordon-Salant, Sandra2; Yanjanin, Nicole3; Zalewski, Christopher1; Houser, Ari4; Porter, Forbes D.3; Brewer, Carmen C.1

Ear & Hearing:
doi: 10.1097/AUD.0b013e3182a362b8
Research Articles

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.

In Brief

Niemann-Pick disease, type C1 (NPC1) is a rare autosomal recessive lysosomal lipidosis resulting in a progressive and fatal neurological deterioration. There is limited evidence suggesting auditory dysfunction as an aspect of the phenotype, but one that is poorly understood and, likely, under reported. Data from 50 patients with NPC1 confirm a prevalent, often high frequency, hearing loss that is progressive in at least some individuals. Retrocochlear involvement is common, and some patients present with a profile of auditory neuropathy spectrum disorder.

Author Information

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.

This work was supported, in part, by a National Institutes of Health (NIH) training grant (T32DC000046) to Kelly A. King, and by the intramural divisions of the National Institute on Deafness and Other Communication Disorders and the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Further support came from a Bench-to-Bedside award from the NIH Office of Rare diseases and the NIH Clinical Research Center, and from both the Ara Parseghian Medical Research Foundation and Dana’s Angels Research Trust.

The authors declare no conflicts of interest.

Address for correspondence: Carmen Crowell Brewer, Department of Health and Human Services, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, 10 Center Drive, Bldg 10/5C306, Bethesda, MD 20892, USA. E-mail:

© 2014 by Lippincott Williams & Wilkins