Effects of CoQ10 Replacement Therapy on the Audiological Characteristics of Pediatric Patients with COQ6 Variants.

Primary coenzyme Q10 (CoQ10) deficiency refers to a group of mitochondrial cytopathies caused by genetic defects in CoQ10 biosynthesis. Primary coenzyme Q10 deficiency-6 (COQ10D6) is an autosomal recessive disorder attributable to biallelic COQ6 variants; the cardinal phenotypes are steroid-resistant nephrotic syndrome (SRNS), which inevitably progresses to kidney failure, and sensorineural hearing loss (SNHL). Here, we describe the phenotypes and genotypes of 12 children with COQ10D6 from 11 unrelated Korean families and quantitatively explore the beneficial effects of CoQ10 replacement therapy on SNHL. A diagnosis of SRNS generally precedes SNHL documentation. COQ10D6 is associated with progressive SNHL. Four causative COQ6 variants were identified in either homozygotes or compound heterozygotes: c.189_191delGAA, c.484C>T, c.686A>C, and c.782C>T. The response rate (no further hearing loss or improvement) was 42.9%; CoQ10 replacement therapy may thus limit and even improve hearing loss. Notably, the audiological benefit appeared to be genotype-specific, suggesting a genotype-phenotype correlation. The results of cochlear implantation were generally favorable, and the effects were sustained over time. Our results thus propose the beneficial effects of CoQ10 replacement therapy on hearing loss. Our work with COQ10D6 patients is a good example of personalized, genetically tailored, audiological rehabilitation of patients with syndromic deafness.