Dataset Information

Longitudinal hearing loss in Wolfram syndrome.

ABSTRACT:

Background

Wolfram syndrome (WFS) is a rare autosomal recessive disease with clinical manifestations of diabetes mellitus (DM), diabetes insipidus (DI), optic nerve atrophy (OA) and sensorineural hearing loss (SNHL). Although SNHL is a key symptom of WFS, there is limited information on its natural history using standardized measures. Such information is important for clinical care and determining its use as an outcome measure in clinical trials.

Methods

Standardized audiologic measures, including pure-tone testing, tympanometry, speech perception, and the unaided Speech Intelligibility Index (SII) were assessed in patients with confirmed WFS annually. Mixed model analyses were used to examine main effects of age, time or interactions for pure tone average (PTA), high frequency average (HFA) and SII.

Results

Forty WFS patients were evaluated between 1 and 6 times. Mean age at initial enrollment was 13.5 years (SD?=?5.6). Patients were classified as having normal hearing (n =?10), mild-to-severe (n =?24) or profound SNHL (n =?6). Mean age of diagnosis for SNHL was 8.3 years (SD?=?5.1) with 75% prevalence. HFA worsened over time for both ears, and SII worsened over time in the worse ear, with greater decline in both measures in younger patients. Average estimated change over 1 year for all measures was in the subclinical range and power analyses suggest that 100 patients would be needed per group (treatment vs. placebo) to detect a 60% reduction in annual change of HFA over 3 years. If trials focused on just those patients with SNHL, power estimates suggest 55 patients per group would be sufficient.

Conclusions

Most patients had a slow progressive SNHL emerging in late childhood. Change over time with standard audiologic tests (HFA, SII) was small and would not be detectable for at least 2 years in an individual. Relatively large sample sizes would be necessary to detect significant impact on hearing progression in a clinical trial. Hearing function should be monitored clinically in WFS to provide appropriate intervention. Because SNHL can occur very early in WFS, audiologists and otolaryngologists should be aware of and refer for later emerging symptoms.

SUBMITTER: Karzon R

PROVIDER: S-EPMC6020390 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Publications

Longitudinal hearing loss in Wolfram syndrome.

Karzon Roanne R Narayanan Anagha A Chen Ling L Lieu Judith E C JEC Hershey Tamara T

Orphanet journal of rare diseases 20180627 1

<h4>Background</h4>Wolfram syndrome (WFS) is a rare autosomal recessive disease with clinical manifestations of diabetes mellitus (DM), diabetes insipidus (DI), optic nerve atrophy (OA) and sensorineural hearing loss (SNHL). Although SNHL is a key symptom of WFS, there is limited information on its natural history using standardized measures. Such information is important for clinical care and determining its use as an outcome measure in clinical trials.<h4>Methods</h4>Standardized audiologic me ...[more]

PMID: 29945639

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Project description:ImportanceBecause hearing loss is highly prevalent and treatable, determining its association with morbidity has major public health implications for disease prevention and the maintenance of health in adults with hearing loss.ObjectiveTo investigate the association between the diagnosis of incident hearing loss and medical comorbidities in adults 50 years or older.Design, setting, and participantsRetrospective, propensity-matched cohort study using administrative claims data from commercially insured and Medicare Advantage members in a geographically diverse US health plan. Adults 50 years or older with claims for services rendered from January 1, 2000, to December 31, 2016, were observed for 2 (n = 154 414), 5 (n = 44 852), and 10 (n = 4728) years. This research was conceptualized and data were analyzed between September 2016 and November 2017.ExposuresA claim for incident hearing loss is defined as 2 claims for hearing loss within 2 consecutive years without evidence of hearing device use, excluding claims for sudden hearing loss or hearing loss secondary to medical conditions.Main outcomes and measuresIncident claims for dementia, depression, accidental falls, nonvertebral fractures, acute myocardial infarction, and stroke.ResultsAfter cohort matching, 48% of participants were women (n = 74 464), 61% were white (n = 93 442), and 31% (n = 48 056) were Medicare Advantage insured, with a mean (SD) age of 64 (10) years. In a multivariate-adjusted modified Poisson regression with robust standard errors, relative associations were strongest for dementia (relative risk at 5 years, 1.50; 95% CI, 1.38-1.64) and depression (relative risk at 5 years, 1.41; 95% CI, 1.26-1.58). The absolute risk of all outcomes was greater in persons with hearing loss than in those without hearing loss at all times, with the greatest risk difference observed at 10 years for all outcomes. The 10-year risk attributable to hearing loss was 3.20 per 100 persons (95% CI, 1.76-4.63) for dementia, 3.57 per 100 persons (95% CI, 1.67-5.47) for falls, and 6.88 per 100 persons (95% CI, 4.62-9.14) for depression.Conclusions and relevanceIn this large observational study using administrative claims data, incident untreated hearing loss was associated with greater incident morbidity than no hearing loss across a range of health conditions. Future studies are needed to elucidate the mechanisms underlying these associations and to determine if treatment for hearing loss could reduce the risk of comorbidity.

Project description:Presbyacusis, or age-related hearing loss, can be characterized in humans as metabolic and sensory phenotypes, based on patterns of audiometric thresholds that were established in animal models. The metabolic phenotype is thought to result from deterioration of the cochlear lateral wall and reduced endocochlear potential that decreases cochlear amplification and produces a mild, flat hearing loss at lower frequencies coupled with a gradually sloping hearing loss at higher frequencies. The sensory phenotype, resulting from environmental exposures such as excessive noise or ototoxic drugs, involves damage to sensory and non-sensory cells and loss of the cochlear amplifier, which produces a 50-70 dB threshold shift at higher frequencies. The mixed metabolic + sensory phenotype exhibits a mix of lower frequency, sloping hearing loss similar to the metabolic phenotype, and steep, higher frequency hearing loss similar to the sensory phenotype. The current study examined audiograms collected longitudinally from 343 adults 50-93 years old (n = 686 ears) to test the hypothesis that metabolic phenotypes increase with increasing age, in contrast with the sensory phenotype. A Quadratic Discriminant Analysis (QDA) was used to classify audiograms from each of these ears as (1) Older-Normal, (2) Metabolic, (3) Sensory, or (4) Metabolic + Sensory phenotypes. Although hearing loss increased systematically with increasing age, audiometric phenotypes remained stable for the majority of ears (61.5 %) over an average of 5.5 years. Most of the participants with stable phenotypes demonstrated matching phenotypes for the left and right ears. Audiograms were collected over an average period of 8.2 years for ears with changing audiometric phenotypes, and the majority of those ears transitioned to a Metabolic or Metabolic + Sensory phenotype. These results are consistent with the conclusion that the likelihood of metabolic presbyacusis increases with increasing age in middle to older adulthood.

Dataset Information

Longitudinal hearing loss in Wolfram syndrome.

Background

Methods

Results

Conclusions

Publications

Longitudinal hearing loss in Wolfram syndrome.

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