Hearing loss in infantile Pompe's disease and determination of underlying pathology in the knockout mouse.
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.
Kamphoven
Joep H J
JH
Department of Neuroscience, Erasmus Medical Centre, Rotterdam, The Netherlands.
de Ruiter
Martijn M
MM
Winkel
Leon P F
LP
Van den Hout
Hannerieke M P
HM
Bijman
Jan
J
De Zeeuw
Chris I
CI
Hoeve
Hans L
HL
Van Zanten
Bert A
BA
Van der Ploeg
Ans T
AT
Reuser
Arnold J J
AJ
D000161:Acoustic Stimulation / Q000379:methods; D000293:Adolescent; D000328:Adult; D000818:Animals; D002648:Child; D002675:Child, Preschool; D003051:Cochlea / Q000473:pathology*; D004195:Disease Models, Animal; D016057:Evoked Potentials, Auditory, Brain Stem / Q000235:genetics; D006009:Glycogen Storage Disease Type II / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D034381:Hearing Loss / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D051379:Mice; D018345:Mice, Knockout