Hearing Loss Related to Gene Mutations in Distal Renal Tubular Acidosis

Abstract

<b><i>Introduction:</i></b> Distal renal tubular acidosis (dRTA) is a disease that may develop either primarily or secondarily, resulting from urinary acidification defects in distal tubules. Hearing loss may accompany primary forms of dRTA. This study aims to determine the characteristics of hearing loss due to different gene mutations in patients with dRTA. <b><i>Methods:</i></b> Behavioral and electrophysiological audiological evaluations were performed after otolaryngology examination in 21 patients with clinically diagnosed dRTA. Radiological imaging of the inner ear (<i>n</i> = 9) was conducted and results of genetic analyses using next-generation sequencing method (<i>n</i> = 16) were included. <b><i>Results:</i></b> Twenty-one patients with dRTA from 20 unrelated families, aged between 8 months and 33 years (median = 12, interquartile range = 20), participated. All patients with <i>ATP6V1B1</i> mutations (<i>n</i> = 9) had different degrees of hearing loss. There was one patient with hearing loss in patients with <i>ATP6V0A4</i> mutations (<i>n</i> = 6). One patient with the <i>WDR72</i> mutation had normal hearing. Large vestibular aqueduct syndrome (LVAS) was detected in 6 (67%) of 9 patients whose radiological evaluation results were available. <b><i>Conclusions:</i></b> LVAS is common in patients with dRTA and may influence the type and severity of hearing loss in these patients. The possibility of both congenital and late-onset and progressive hearing loss should be considered in dRTA patients. A regular audiological follow-up is essential for the early detection of a possible late-onset or progressive hearing loss in these patients.

Electrophysiological characterization of a Cav3.2 calcium channel missense variant associated with epilepsy and hearing loss

“…While the alterations may seem relatively mild, they have the merit to be observed and will require further experimentation to define their meaning in terms of pathogenicity. Clearly, there is evidence that alteration of pH homeostasis in response to primary metabolic disorders such as renal tubular acidosis is often accompanied with sensorineural hearing alterations [15]. In such context, altered pH e -dependent modulation of Ca v 3.2 by the R132H mutation may represent a risk factor for hearing loss.…”