Abstract
OBJECTIVES: Peroxisome Biogenesis Disorders in the Zellweger Spectrum (PBD-ZSD) are autosomal recessive disorders characterized by defects in peroxisome function, biosynthesis, and/or assembly. Despite its frequent documentation, hearing loss associated with PBD-ZSD has not been extensively characterized. The purpose of this retrospective natural history study was to better characterize the hearing loss associated with PBD-ZSD and to provide additional insight into the evaluation and management of PBD-ZSD patients with hearing loss. DESIGN: Audiological data from medical records of 42 patients with PBD-ZSD or D-bifunctional protein deficiency were collected from an ongoing longitudinal retrospective natural history study. An initial dataset of 300 audiograms and/or audiometric test results from the 42 patients were used to characterize the degree of hearing loss, type of hearing loss, relationships between air and bone conduction thresholds, age-related changes in hearing loss, and benefit with amplification. RESULTS: The majority of PBD-ZSD patients in this study presented with moderately-severe to severe hearing loss and relatively slow rates of longitudinal changes in hearing sensitivity. Improvements in hearing thresholds were observed with use of hearing aid amplification. Though bone conduction data were limited, air-bone gaps and air conduction threshold fluctuations observed in several patients suggest there may be an increased occurrence of mixed hearing losses in PBD-ZSD populations. CONCLUSION: The results of this retrospective study provide insight into the hearing loss associated with PBD-ZSD, but also emphasize the need for more complete assessments of hearing loss type and middle ear function in these patients. The addition of more comprehensive datasets to the ongoing natural history study will enhance our understanding of the pathophysiology underlying PBD-ZSD and guide the development of targeted evaluation and management recommendations for patients with PBD-ZSD.