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Cardiac and renal dysfunction is associated with progressive hearing loss in patients with Fabry disease.

ABSTRACT: Fabry disease (FD) is an X-linked recessive hereditary lysosomal storage disorder which results in the accumulation of globotriaosylceramid (Gb3) in tissues of kidney and heart as well as central and peripheral nervous system. Besides prominent renal and cardiac organ involvement, cochlear symptoms like high-frequency hearing loss and tinnitus are frequently found with yet no comprehensive data available in the literature.To examine hearing loss in patients with FD depending on cardiac and renal function.Single-center study with 68 FD patients enrolled between 2012 and 2016 at the Department of Oto-Rhino-Laryngology, Plastic, Aesthetic and Reconstructive Head and Neck Surgery of the University of Würzburg. Every subject underwent an oto-rhino-laryngological examination as well as behavioral, electrophysiological and electroacoustical audiological testing. High-frequency thresholds were evaluated by using a modified PTA6 (0.5, 1, 2, 4, 6, 8) and HF-PTA (6, 8 kHz). Renal function was measured by eGFR, cardiac impairment was graduated by NYHA class.Sensorineural hearing loss was detected in 58.8% of the cohort, which occurred typically in sudden episodes and affected especially high frequencies. Hearing loss is asymmetric, beginning unilaterally and affecting the contralateral ear later. Tinnitus was reported by 41.2%. Renal and cardiac impairment influenced the severity of hearing loss (p < 0.05).High frequency hearing loss is a common problem in patients with FD. Although not life-threatening, it can seriously reduce quality of life and should be taken into account in diagnosis and therapy. Optimized extensive hearing assessment including higher frequency thresholds should be used.

SUBMITTER: Koping M

PROVIDER: S-EPMC5697846 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Cardiac and renal dysfunction is associated with progressive hearing loss in patients with Fabry disease.

Köping Maria M Shehata-Dieler Wafaa W Cebulla Mario M Rak Kristen K Oder Daniel D Müntze Jonas J Nordbeck Peter P Wanner Christoph C Hagen Rudolf R Schraven Sebastian S

PloS one 20171121 11

<h4>Background</h4>Fabry disease (FD) is an X-linked recessive hereditary lysosomal storage disorder which results in the accumulation of globotriaosylceramid (Gb3) in tissues of kidney and heart as well as central and peripheral nervous system. Besides prominent renal and cardiac organ involvement, cochlear symptoms like high-frequency hearing loss and tinnitus are frequently found with yet no comprehensive data available in the literature.<h4>Objective</h4>To examine hearing loss in patients w ...[more]

PMID: 29161295

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Project description:BACKGROUND:Hearing loss (HL) is a well-known feature of Fabry disease (FD). Its presence and characteristics have mainly been studied in adult patients, while only limited data are available on the presence and degree of HL in children with FD. This prompted us to study hearing sensitivity in pediatric FD patients. METHODS:All available audiograms of the Dutch and Norwegian children with FD were retrospectively collected. First, hearing sensitivity was determined by studying hearing thresholds at low, high, and ultra-high frequencies in children with FD and comparing them to zero dB HL, i.e., healthy children. In addition, the presence and type of slight/mild HL (defined as hearing thresholds at low frequencies of 25-40 dB HL) and moderate to severe HL (hearing thresholds >40 dB HL) at first visit were analyzed. If available, follow-up data were used to estimate the natural course of hearing sensitivity and HL in children with FD. RESULTS:One-hundred-thirteen audiograms of 47 children with FD (20 boys, median age at first audiogram 12.0 (range 5.1-18.0) years) were analyzed. At baseline, slight/mild or moderate to severe HL was present in three children (6.4%, 2 boys). Follow-up measurements showed that three additional children developed HL before the age of 18. Of these six children, five had sensorineural HL, most likely caused by FD. Compared to healthy children (zero dB HL), FD children showed increased hearing thresholds at all frequencies (p < 0.01), which was most prominent at ultra-high frequencies (>8 kHz). Hearing sensitivity at these ultra-high frequencies deteriorated in a period of 5 years of follow-up. CONCLUSION:A minority of children with FD show slight/mild or moderate to severe HL, but their hearing thresholds are poorer than the reference values for normal-hearing children. Clinical trials in FD children should demonstrate whether HL can be prevented or reversed by early treatment and should specifically study ultra-high frequencies.

Project description:Fabry disease, OMIM 301500, is a progressive multisystem storage disorder due to the deficiency of alpha-galactosidase A (GALA). Neurological and vascular manifestations of this disorder with regard to hearing loss have not been analysed quantitatively in large cohorts. We conducted a retrospective cross sectional analysis of hearing loss in 109 male and female patients with Fabry disease who were referred to and seen at the Clinical Center of the National Institutes of Health, Bethesda, MD, USA on natural history and enzyme replacement study protocols. There were 85 males aged 6-58 years (mean 31 years, SD 13) and 24 females aged 22-72 years (mean 42 years, SD 12). All patients underwent a comprehensive audiological evaluation. In addition, cerebral white matter lesions, peripheral neuropathy, and kidney function were quantitatively assessed. HL(95), defined as a hearing threshold above the 95th percentile for age and gender matched normal controls, was present in 56% [95% CI (42.2-67.2)] of the males. Prevalence of HL(95) was lower in the group of patients with residual GALA enzyme activity compared with those without detectable activity (33% versus 63%) HL(95) was present in the low-, mid- and high-frequency ranges for all ages. Male patients with HL(95) had a higher microvascular cerebral white matter lesion load [1.4, interquartile range (IQR) 0-30.1 +/- versus 0, IQR 0-0], more pronounced cold perception deficit [19.4 +/- 5.5 versus 13.5 +/- 5.5 of just noticeable difference (JND) units] and lower kidney function [creatinine: 1.6 +/- 1.2 versus 0.77 +/- 0.2 mg/dl; blood urea nitrogen (BUN): 20.1 +/- 14.1 versus 10.3 +/- 3.28 mg/dl] than those without HL(95) (P < 0.001). Of the females, 38% had HL(95). There was no significant association with cold perception deficit, creatinine or BUN in the females. Word recognition and acoustic reflexes analyses suggested a predominant cochlear involvement. We conclude that hearing loss involving all frequency regions significantly contributes to morbidity in patients with Fabry disease. Our quantitative analysis suggests a correlation of neuropathic and vascular damage with hearing loss in the males. Residual GALA activity appears to have a protective effect against hearing loss.

Project description:BACKGROUND:Fabry disease (FD) is a lysosomal storage disorder resulting in systemic accumulation of globotriaosylceramide resulting in multi-organ dysfunction e.g. cerebral, cardiac, renal and audiologic complications. The audiologic involvement in FD has often been neglected; while not a lethal aspect of the disease, hearing loss can have a significantly negative impact on quality of life. OBJECTIVES:To investigate baseline hearing status of the Danish Fabry cohort prior to treatment, compared to sex- and age-expected hearing levels and correlating hearing to renal and cerebral findings. MATERIAL AND METHODS:Retrospective study of baseline hearing status of the Danish Fabry cohort (n = 83, 9-72 years). Air conduction and speech discrimination scores were assessed at 6 frequencies between 0.25-8 kHz bilaterally. Data were collected between 2001-2014 and compiled in STATA using multilinear mixed modelling for statistical evaluation. RESULTS:Hearing thresholds at all frequencies deviated from the expected thresholds of an otologically normal cohort (p<0.001) and ranged 0.5 to 1.5 standard deviations below expected values. In total 29 males and 54 females were included. Hearing loss was more pronounced in the higher frequencies. There was a trend of association between hearing loss and measured glomerular filtration rate (mGFR) (p = 0.084). No association was present between hearing loss and albuminuria (p = 0.90), Fabry related cerebral abnormalities (p = 0.84) and cardiac left ventricular mass index, (LVMi) (p = 0.67) independent of sex. Hearing thresholds were poorer for men compared to women (p = 0.001). Sex differences were present at 0.25, 4 and 8 kHz. CONCLUSION:Our findings demonstrated significant hearing loss in Danish FD patients before treatment initiation, being more profound than in otologically healthy individuals at all frequencies. Additionally, we observed no association between hearing loss and LVMi, albuminuria or FD cerebral abnormalities, with a trend of association to mGFR. SYNOPSIS:Patients with Fabrys disease have hearing loss of all frequencies and most prominently at high frequencies (4-8 kHz), with no association between the hearing loss and cerebral abnormalities, and cardiac mass but with a trend of association to measured glomerular filtration rate.

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Cardiac and renal dysfunction is associated with progressive hearing loss in patients with Fabry disease.

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Cardiac and renal dysfunction is associated with progressive hearing loss in patients with Fabry disease.

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