ubiquinone and Hearing-Loss--Sensorineural

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

Topics: Ataxia; Deafness; Hearing Loss, Sensorineural; Humans; Mitochondrial Diseases; Muscle Weakness; Nephrotic Syndrome; Steroids; Ubiquinone

CoenzymeQ10 is one of the main cellular antioxidants and an essential lipid involved in numerous cell reactions, such as energy production and apoptosis modulation. A large number of enzymes are involved in CoQ10 biosynthesis. Mutations in the genes encoding for these enzymes cause a CoQ10 deficiency, characterized by neurological and systemic symptoms. Here we describe two young sisters with sensorineural deafness followed by optic atrophy, due to a novel homozygous pathogenic variant in PDSS1. The visual system seems to be mainly involved when the first steps of CoQ10 synthesis are impaired (PDSS1, PDSS2, and COQ2 deficiency).

Topics: Adolescent; Alkyl and Aryl Transferases; Ataxia; Child; Consanguinity; Female; Hearing Loss, Sensorineural; Humans; Mitochondrial Diseases; Muscle Weakness; Mutation, Missense; Optic Atrophies, Hereditary; Ubiquinone

Mitochondrial NADP

Topics: Animals; Apoptosis; Biomarkers; Disease Models, Animal; Fluorescent Antibody Technique; Hair Cells, Auditory; Hearing Loss, Sensorineural; Homozygote; Immunohistochemistry; Isocitrate Dehydrogenase; Mice; Mice, Knockout; Mitochondria; Organophosphorus Compounds; Oxidation-Reduction; Oxidative Stress; Reactive Oxygen Species; Spiral Ganglion; Ubiquinone

The phenotypic combination of steroid-resistant focal segmental glomerulosclerosis (SR-FSGS) and sensorineural hearing loss has been mainly reported in patients with mitochondrial cytopathies, including primary coenzyme Q10 (CoQ10) deficiency. In this report of 10 children with SR-FSGS and sensorineural hearing loss, we found 6 patients with biallelic COQ6 mutations. Median age at the onset of nephrotic syndrome was 29 (range, 15-47) months. All patients progressed to end-stage renal disease within a median of 13 (range, 1-27) months after the onset. Kidney biopsy revealed abnormal mitochondrial proliferation in podocytes in all 6 patients. None of the 5 patients who underwent kidney transplantation developed recurrence of FSGS. Primary CoQ10 deficiency due to COQ6 mutations should be considered in children presenting with both SR-FSGS and sensorineural hearing loss. An early diagnosis of COQ6 mutations is essential because the condition is treatable when CoQ10 supplementation is started at the early stage. We recommend early kidney biopsy because detection of abnormal mitochondrial proliferation in podocytes might provide an earlier diagnostic clue.

Topics: Child, Preschool; Female; Glomerulosclerosis, Focal Segmental; Hearing Loss, Sensorineural; Humans; Infant; Male; Mutation; Ubiquinone

Steroid-resistant nephrotic syndrome (SRNS) is a frequent cause of end-stage renal failure. Identification of single-gene causes of SRNS has generated some insights into its pathogenesis; however, additional genes and disease mechanisms remain obscure, and SRNS continues to be treatment refractory. Here we have identified 6 different mutations in coenzyme Q10 biosynthesis monooxygenase 6 (COQ6) in 13 individuals from 7 families by homozygosity mapping. Each mutation was linked to early-onset SRNS with sensorineural deafness. The deleterious effects of these human COQ6 mutations were validated by their lack of complementation in coq6-deficient yeast. Furthermore, knockdown of Coq6 in podocyte cell lines and coq6 in zebrafish embryos caused apoptosis that was partially reversed by coenzyme Q10 treatment. In rats, COQ6 was located within cell processes and the Golgi apparatus of renal glomerular podocytes and in stria vascularis cells of the inner ear, consistent with an oto-renal disease phenotype. These data suggest that coenzyme Q10-related forms of SRNS and hearing loss can be molecularly identified and potentially treated.

Topics: Animals; Child; Child, Preschool; Chlorocebus aethiops; COS Cells; Hearing Loss, Sensorineural; HeLa Cells; Homozygote; Humans; Infant; Infant, Newborn; Intracellular Signaling Peptides and Proteins; Kidney Glomerulus; Laminin; Membrane Proteins; Mutation; Nephrotic Syndrome; Phenotype; Podocytes; Rats; Ubiquinone; WT1 Proteins; Zebrafish

We investigated the association of idiopathic sudden sensorineural hearing loss (ISSNHL) with coenzyme Q (CoQ) and cardiovascular risk factors.. A prospective study.. Hospital center.. Thirty Italian patients with ISSNHL and 60 healthy Italian subjects.. Diagnostic.. Evaluation of serum CoQ levels and cardiovascular risk factors (total cholesterol, low-density lipoprotein [LDL], homocysteine [HCY]). The results were compared with variance analysis and Student's t test. Univariate and multivariate analysis were used to evaluate the association between ISSNHL and CoQ, total cholesterol, LDL, and HCY levels.. In our series, we found a significant association between ISSNHL and high total cholesterol (p < 0.05), high LDL (p = 0.021), and low CoQ (p < 0.05) levels. We did not find a significant association between ISSNHL and HCY levels. In the univariate analysis, low levels of CoQ, high levels of total cholesterol, and LDL were found to be significantly associated with ISSNHL. In the multivariate analysis, only high levels of total cholesterol and low levels of CoQ remained significantly associated with a high risk of sudden sensorineural hearing loss.. The studies regarding the role of cardiovascular risk factors in ISSNHL are not conclusive. This is the first report regarding the association of ISSNHL and low serum levels of the antioxidant CoQ. Further studies are needed to investigate the role of antioxidants, including CoQ, in ISSNHL.

Topics: Adult; Aged; Analysis of Variance; Antioxidants; Audiometry; Cardiovascular Diseases; Cholesterol; Coenzymes; Female; Hearing Loss, Sensorineural; Homocysteine; Humans; Italy; Lipoproteins, LDL; Male; Middle Aged; Prospective Studies; Risk Factors; Ubiquinone

Mutations in mitochondrial DNA are rare etiologies of adult-onset diabetes mellitus (DM) that merit identification to 1) prevent iatrogenic lactic acidosis, 2) prompt appropriate screening of affected patients and their families, 3) provide genetic counseling, and 4) provide an opportunity to investigate strategies for preventing diabetes.. The objective of this study is to raise awareness of this rare form of adult-onset nonobese DM so that these patients are identified and provided with appropriate care.. We describe a kindred in which four of seven siblings have adult-onset DM and sensorineural hearing loss with a confirmed genetic mutation at position 3243 in the tRNA. Two other siblings in this kindred demonstrate different phenotypes of mitochondrial disease.. The proband was treated with coenzyme Q10 for 1 yr.. Outcome measures included stress thallium exercise testing and audiometry testing.. After 1 yr of treatment of with coenzyme Q10, repeat stress thallium testing demonstrated improvement in the exercise tolerance of the proband from 7-12 min. Audiometry testing did not demonstrate a change in the rate of hearing decline.. Maternally inherited diabetes and deafness is a rare cause of DM that is important to diagnose because of the unique management issues and associated comorbidities. This work highlights clues to the identification of this rare monogenic form of adult- onset diabetes.

Topics: Adult; Coenzymes; Diabetes Mellitus, Type 2; Exercise Test; Female; Genes, X-Linked; Hearing Loss, Sensorineural; Humans; Mitochondrial Diseases; Models, Biological; North America; Pedigree; RNA, Transfer, Leu; Ubiquinone

CoQ 10 may be helpful in delaying the progression of hearing loss in patients with the 7445A-->G mitochondrial mutation. Objective. To assess the effect of an antioxidant drug (Coenzyme Q-10) on the hearing level of patients with the mitochondrial DNA 7445A-->G mutation and associated sensorineural hearing loss (SNHL). Material and methods. We identified three patients with bilateral non-syndromic SNHL harboring the mitochondrial 7445A-->G mutation. Two patients had a family history of hearing loss with a strong matrilineal inheritance. The other patient did not have a family history of hearing loss. Two patients (1 with familial and 1 with sporadic SNHL) received treatment with 75 mg of Coenzyme Q-10 (CoQ10) twice a day for 1 year. The remaining patient with a familial form of hearing loss did not agree to take the treatment. Average bone conduction pure-tone thresholds for 0.5, 1, 2 and 4 kHz were obtained before and after diagnosis of mitochondrial hearing loss, and before and after treatment with CoQ10. Results. CoQ10-treated patients did not show any additional deterioration of their SNHL after 12 (familial case) and 13 months (sporadic case). The progression rate of SNHL was 6 dB/year in the 2 years prior to initiation of treatment in the familial case who received CoQ10 treatment. One year after being diagnosed with mitochondrial hearing loss, the patient who refused CoQ10 treatment exhibited an 11-dB deterioration of his hearing thresholds. There were no side-effects related to treatment with CoQ10.

Topics: Adult; Antioxidants; Coenzymes; Disease Progression; DNA Primers; DNA, Mitochondrial; Female; Hearing Loss, Sensorineural; Humans; Male; Middle Aged; Point Mutation; Ubiquinone

CoQ transfers electrons from complexes I and II of the mitochondrial respiratory chain to complex III. There are very few reports on human CoQ deficiency. The clinical presentation is usually characterized by: epilepsy, muscle weakness, ataxia, cerebellar atrophy, migraine, myogloblinuria and developmental delay. We describe a patient who presented with neonatal liver and pancreatic insufficiency, tyrosinemia and hyperammonemia and later developed sensorineural hearing loss and Leigh syndrome. Liver biopsy revealed markedly reduced complex I+III and II+III. Addition of CoQ to the liver homogenate restored the activities, suggesting CoQ depletion. Histological staining showed prominent bridging; septal fibrosis and widening of portal spaces with prominent mixed inflammatory infiltrate, associated with interface hepatitis, bile duct proliferation with numerous bile plugs. Electron microscopy revealed a large number of mitochondria, which were altered in shape and size, widened and disordered intercristal spaces. This may be the first case of Leigh syndrome with liver and pancreas insufficiency, possibly caused by CoQ responsive oxphos deficiency.

Topics: Biopsy; Electron Transport Complex I; Electron Transport Complex II; Electron Transport Complex III; Hearing Loss, Sensorineural; Humans; Hyperammonemia; Infant; Leigh Disease; Liver; Liver Failure, Acute; Male; Metabolism, Inborn Errors; Mitochondria, Liver; Mitochondrial Diseases; Oxidative Phosphorylation; Pancreas; Ubiquinone

Coenzyme Q10 (CoQ10) has already been favorably evaluated in the clinical treatment of heart disease. In the otolaryngological field, it has been reported that CoQ10 is effective in promoting recovery from acute sudden deafness. However, the pharmakinetics of CoQ10 in the inner ear is not yet clarified. The present study focuses upon the pharmacokinetics of CoQ10 using guinea pigs with acute sensorineural hearing loss artificially induced by hypoxia conditions. The respiration of the animals was controlled in an artificial respirator while the ABR, ECG and blood pressure were monitored. Repeated hypoxia caused a gradual disappearance of the ABR. After the experiments, the animals were sacrificed and brain and inner ear were examined by histological and histochemical methods as well as by SEM and TEM. The results indicated that CoQ10 is effective in promoting recovery from damage in auditory hairs as well as preventing respiratory metabolic impairment of hair cell due to hypoxia.

Topics: Animals; Coenzymes; Evoked Potentials, Auditory; Guinea Pigs; Hair Cells, Auditory; Hearing Loss, Sensorineural; Oxygen; Ubiquinone