Possible mechanisms for sensorineural hearing loss and deafness in patients with propionic acidemia
- PDF / 1,059,025 Bytes
- 4 Pages / 595.276 x 790.866 pts Page_size
- 65 Downloads / 181 Views
LETTER TO THE EDITOR
Open Access
Possible mechanisms for sensorineural hearing loss and deafness in patients with propionic acidemia S. C. Grünert1*, I. Bodi2 and K. E. Odening2 Abstract Propionic acidemia is an inborn error of metabolism caused by deficiency of the mitochondrial enzyme propionylCoA 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. Keywords: Propionic acidemia, Propionic aciduria, Hearing loss, Long QT syndrome, Sensorineural deafness, KvLQT1, KCNE1, Voltage-gated potassium channel, Inner ear Propionic acidemia (PA) is an inborn error of metabolism caused by deficiency of the mitochondrial enzyme propionyl-CoA carboxylase. This enzyme converts propionyl-CoA to D-methylmalonyl-CoA and is involved in the metabolism of branched-chain amino acids, oddnumbered fatty acids, cholesterol side chains, thymine, and uracil [1]. Patients with PA are prone to acute lifethreatening metabolic decompensations with severe metabolic acidosis and hyperammonemia, and most affected children already present with symptoms during the neonatal period. With progression of the disease, long-term complications involving the neurological, cardiological, hematological, immunological and gastrointestinal system are common [2]. One of the main cardiological problems is the development of an acquired long QT syndrome (LQTS), which can be found in up to 70% of patients beyond childhood and puts * Correspondence: [email protected] 1 Center of Pediatrics and Adolescent Medicine, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Mathildenstr. 1, 79106 Freiburg, Germany Full list of author information is available at the end of the article
patients at risk for potentially lethal ventricular arrhythmia [2, 3]. Among the neurological complications, sensorineural hearing impairment has been reported in several patients with PA [2, 4, 5]. In a study with 55 PA patients from Germany, Switzerland and Austria, hearing loss was apparent in 13% of the patients [2]. Similarly, Brosch et al. described 4 patients with PA and sensorineural deafness or severe hearing loss [5]. Mutation analyses of the PCCA and PCCB genes, encoding the two
Data Loading...
