No evidence of hearing loss in pseudohypoaldosteronism type 1 patients.
CONCLUSIONS
The fact that pseudohypoaldosteronism type 1 (PHA-1) patients with a defect in the alpha subunit of epithelial sodium channels (ENaC) in the cochlea have normal hearing suggests compensation by alternative sodium transport mechanisms. Consequently, hearing loss due to defective cochlear transmembrane serine protease TMPRSS3 activity is likely to be related to its effect on proneurotrophin cleavage, indicating an action on neurological components of hearing. The normal hearing of PHA-1 patients with affected mineralocorticoid receptors, together with experimental results in animals, indicates that the mineralocorticoid aldosterone is not the most crucial regulator of sodium transport in the cochlea.


OBJECTIVE
Profound hearing loss has been observed in patients with a defect in transmembrane serine protease TMPRSS3, the presumed activator of ENaCs. Renal ENaCs and their regulators, such as the mineralocorticoid receptors, are present in the cochlear structures involved in hearing. The aim of this study was to investigate whether PHA-1 patients with defects in these channels or regulators suffer from hearing impairment.


METHODS
Pure-tone audiometry was performed in four cases with PHA-1 due to mutations in alphaENaC (n=2) or mineralocorticoid receptor (n=2).


RESULTS
All examined cases had normal hearing at all tested frequencies.
Peters
Theo A
TA
Department of Otorhinolaryngology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. t.peters@kno.umcn.nl
Levtchenko
Elena
E
Cremers
Cor W R J
CW
Curfs
Jo H A J
JH
Monnens
Leo A H
LA
D000328:Adult; D001301:Audiometry, Pure-Tone; D002648:Child; D053503:Epithelial Sodium Channels; D005260:Female; D006319:Hearing Loss, Sensorineural / Q000175:diagnosis*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D011546:Pseudohypoaldosteronism / Q000175:diagnosis* / Q000235:genetics; D012016:Reference Values; D018570:Risk Assessment; D012494:Sampling Studies; D012680:Sensitivity and Specificity; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism*
D053503:Epithelial Sodium Channels; D015222:Sodium Channels