Comprehensive analysis of hearing function in Morquio A syndrome: Implications for diagnosis and management

Morquio A syndrome (mucopolysaccharidosis IVA) is a lysosomal storage disorder characterized by systemic skeletal dysplasia and multisystem involvement. Hearing loss is frequently reported but remains insufficiently characterized, with few studies incorporating comprehensive behavioral and electrophysiologic assessments. In this prospective study, the largest Morquio A auditory cohort to date, participants underwent detailed audiologic and imaging testing at Nemours Children's Health as part of the National Institutes of Health-sponsored natural history program. Assessments included pure-tone thresholds, speech-recognition thresholds, speech perception in quiet and noise, tympanometry, distortion-product otoacoustic emissions, auditory brainstem responses, and cortical auditory evoked potentials. Outcomes included the prevalence, type, and severity of hearing loss, as well as associations with age and clinical disease severity. Hearing loss was identified in 50.9% of 56 patients, with sensorineural loss more frequent than conductive or mixed types. Prevalence of hearing loss was significantly correlated with clinical severity (height percentile), whereas no significant correlation was observed between hearing loss severity and diagnostic age. Reduced or absent otoacoustic emissions with preserved brainstem and cortical responses indicate predominant cochlear involvement with potential secondary central contributions. Comprehensive imaging of the middle and inner ear showed no significant structural differences between patients with and without hearing loss. Hearing loss is common in Morquio A and is primarily sensorineural. The absence of associations with age or disease severity underscores the heterogeneity of auditory involvement. These findings emphasize the need for routine, comprehensive audiologic monitoring to support early detection and mitigate long-term impacts on communication and quality of life.