Possible mechanisms for sensorineural hearing loss and deafness in patients with propionic acidemia

Propionic acidemia is an inborn error of metabolism caused by deficiency of the mitochondrial enzyme propionyl-CoA carboxylase. Sensorineural deafness and severe hearing loss have been described as long-term complications of this disease, however, the mechanism has not yet been elucidated. We have r...

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Bibliographic Details
Published in:Orphanet journal of rare diseases 2017-02, Vol.12 (1), p.30-30, Article 30
Main Authors: Grünert, S C, Bodi, I, Odening, K E
Format: Article
Language:English
Subjects:
Animals
Gene Expression Regulation - physiology
Hearing Loss, Sensorineural - etiology
Hearing Loss, Sensorineural - metabolism
Humans
KCNQ1 Potassium Channel - genetics
KCNQ1 Potassium Channel - metabolism
Letter to the Editor
Medical research
Mice
Potassium Channels, Voltage-Gated - genetics
Potassium Channels, Voltage-Gated - metabolism
Propionic Acidemia - complications
Rare diseases
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Summary:Propionic acidemia is an inborn error of metabolism caused by deficiency of the mitochondrial enzyme propionyl-CoA carboxylase. Sensorineural deafness and severe hearing loss have been described as long-term complications of this disease, however, the mechanism has not yet been elucidated. We have recently shown by patch clamping experiments and Western blots that acute and chronic effects of accumulating metabolites such as propionic acid, propionylcarnitine and methylcitrate on the KvLQT1/KCNE1 channel complex cause long QT syndrome in patients with propionic acidemia by inhibition of K flow via this channel. The same KvLQT1/KCNE1 channel complex is expressed in the inner ear and essential for luminal potassium secretion into the endolymphatic space. A disruption of this K flow results in sensorineural hearing loss or deafness. It can be assumed that acute and chronic effects of accumulating metabolites on the KvLQT1/KCNE1 channel protein may similarly cause the hearing impairment of patients with propionic acidemia.
ISSN:1750-1172
1750-1172
DOI:10.1186/s13023-017-0585-5