Related Experiment Video
Updated: Aug 23, 2026
Evaluation of Planar-Cell-Polarity Phenotypes in Ciliopathy Mouse Mutant Cochlea
Published on: February 21, 2016
Hearing loss in infantile Pompe's disease and determination of underlying pathology in the knockout mouse
Joep H J Kamphoven1, Martijn M de Ruiter, Leon P F Winkel
1Department of Neuroscience, Erasmus Medical Centre, Rotterdam, The Netherlands.
Insights
Hearing loss is a newly identified symptom in infantile Pompe's disease. Glycogen storage in the cochlea causes this hearing deficit, distinguishing it from juvenile forms.
Area of Science:
- Genetics and Molecular Biology
- Otolaryngology
- Neurology
Background:
- Hearing impairment is a known symptom of various lysosomal storage disorders.
- Hearing loss has not previously been recognized as a clinical manifestation of Pompe's disease (glycogen storage disease type II).
Purpose of the Study:
- To investigate the occurrence and underlying mechanisms of hearing loss in infantile Pompe's disease.
- To determine if hearing impairment is a characteristic feature of the infantile subtype.
Main Methods:
- Auditory brainstem response (ABR) testing and oto-acoustic emission measurements were performed on patients.
- A knockout mouse model of Pompe's disease was used to examine cochlear pathology at a cellular level.
Main Results:
- Four infants with infantile Pompe's disease exhibited significant hearing loss (30-90 dB).
- ABR results indicated pathology in the middle or inner ear, not the central auditory system.
- Glycogen accumulation was found in cochlear hair cells, supporting cells, stria vascularis, and spiral ganglion cells in the mouse model.
Conclusions:
- Cochlear pathology due to glycogen storage is the likely cause of hearing loss in infantile Pompe's disease.
- Hearing deficit may be a characteristic feature distinguishing infantile Pompe's disease from juvenile forms.
Abstract:
Hearing deficit occurs in several lysosomal storage disorders but has so far not been recognized as a symptom of Pompe's disease (glycogen storage disease type II). We discovered quite unexpectedly 30-90 dB hearing loss in four infants with Pompe's disease, who participated in a study on the safety and efficacy of enzyme replacement therapy. Three other patients with juvenile Pompe's disease did not have this symptom. The ABR (auditory brainstem response) thresholds but not the interpeak latency times were increased. This pointed to middle or inner ear pathology rather than to involvement of the central auditory nervous system. The possible occurrence of cochlear pathology was supported by the absence of oto-acoustic emissions. We investigated this hypothesis in a knockout mouse model of Pompe's disease and found glycogen storage in the inner and outer hair cells of the cochlea, the supporting cells, the stria vascularis, and the spiral ganglion cells. We conclude that cochlear pathology is the most likely cause of hearing loss in infantile Pompe's disease and possibly a characteristic feature of this clinical subtype.
