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

Köping, M; Shehata‐Dieler, Wafaa; Cebulla, Mario; Rak, Kristen; Oder, Daniel; Müntze, Jonas; Nordbeck, Peter; Wanner, Christoph; Hagen, Rudolf; Schraven, Sebastian P.

doi:10.1371/journal.pone.0188103

Cited by 13 publications

(17 citation statements)

References 24 publications

(39 reference statements)

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“…Hearing loss was most prominent at high frequencies (4, 8 kHz) but also noticeable at the lowest frequency in males (250Hz). Our findings of all frequency hearing loss was partially in concert with previous studies [5,6,22,23].…”

Section: Discussionsupporting

confidence: 92%

Significant hearing loss in Fabry disease: Study of the Danish nationwide cohort prior to treatment

Yazdanfard¹,

Madsen²,

Nielsen³

et al. 2019

PLoS ONE

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BackgroundFabry 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.ObjectivesTo 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 methodsRetrospective 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.ResultsHearing 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.ConclusionOur 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.SynopsisPatients 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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Section: Discussionsupporting

confidence: 92%

Significant hearing loss in Fabry disease: Study of the Danish nationwide cohort prior to treatment

Yazdanfard¹,

Madsen²,

Nielsen³

et al. 2019

PLoS ONE

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“…A confounding presbyacusis could be ruled out. This resembles findings from previous studies [ 32 ].…”

Section: Discussionsupporting

confidence: 92%

“…The severity of hearing loss is significantly correlated to the function and injury of both kidney and the heart [ 32 ]. One limitation might be seen in age-dependency of GFR and NYHA class.…”

Section: Discussionmentioning

confidence: 99%

Characterization of vertigo and hearing loss in patients with Fabry disease

Köping

Shehata‐Dieler

Schneider

et al. 2018

Orphanet J Rare Dis

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BackgroundFabry Disease (FD) is an X-linked hereditary lysosomal storage disorder which leads to a multisystemic intralysosomal accumulation of globotriaosylceramid (Gb3). Besides prominent renal and cardiac organ involvement, patients commonly complain about vestibulocochlear symptoms like high-frequency hearing loss, tinnitus and vertigo. However, comprehensive data especially on vertigo remain scarce. The aim of this study was to examine the prevalence and characteristics of vertigo and hearing loss in patients with FD, depending on renal and cardiac parameters and get hints about the site and the pattern of the lesions.MethodsSingle-center study with 57 FD patients. Every patient underwent an oto-rhino-laryngological examination as well as videonystagmography and vestibular evoked myogenic potentials (VEMPs) and audiological measurements using pure tone audiometry and auditory brainstem response audiometry (ABR). Renal function was measured by eGFR, cardiac impairment was graduated by NYHA class.ResultsMore than one out of three patients (35.1%) complained about hearing loss, 54.4% about vertigo and 28.1% about both symptom. In 74% a sensorineural hearing loss of at least 25 dB was found, ABR could exclude any retrocochlear lesion. Caloric testing showed abnormal values in 71.9%, VEMPs were pathological in 68%. A correlation between the side or the shape of hearing loss and pathological vestibular testing could not be revealed.ConclusionsHearing loss and vertigo show a high prevalence in FD. While hearing loss seems due to a cochlear lesion, peripheral vestibular as well as central nervous pathologies cause vertigo. Thus, both the site of lesion and the pathophysiological patterns seem to differ.Electronic supplementary materialThe online version of this article (10.1186/s13023-018-0882-7) contains supplementary material, which is available to authorized users.

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“…Four subjects (2 men and 2 women) had a history of a previous cerebral stroke: 1 had suffered from embolic strokes in the right median cerebral artery territory, 1 in the posterior cerebral artery area territory without residual symptoms, 1 had a recanalized distal internal carotid artery occlusion with residual aphasia and spastic ride-sided hemiparesis, and 1 an infarction of the rostral brainstem and cerebral hemispheral regions due to cryptogenic embolism in the distal basilar artery. Events suspicious for transitory ischemic attacks or hearing loss [41] were not reported by any subject.…”

Section: Resultsmentioning

confidence: 99%

Clinical impact of the alpha-galactosidase A gene single nucleotide polymorphism -10C>T

et al. 2018

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Single nucleotide polymorphisms (SNPs) in the alpha-galactosidase A gene region (GLA) have been discussed as potential cause of symptoms and organ manifestations similarly to those seen in Fabry disease (FD). However, due to scarce data, clinical implications remain limited. The aim of the present study was to investigate the clinical impact of -10C>T SNP in the GLA.Prospective single-center observational study to determine the natural history and outcome of FD.Subjects initially referred to the Fabry Center for Interdisciplinary Therapy Würzburg (FAZIT) for management of suspected FD (11 women, 2 men, mean age 42 ± 10 years) who were tested negative for coding GLA mutations but positive for the noncoding -10C>T SNP underwent comprehensive characterization for therapy recommendation.All subjects reported at least 1 neurological, but no cardiac or renal symptoms. In 7 patients, pain of unknown etiology was reported and 3 patients had a history of cryptogenic stroke. In all patients, α-GAL activity was at a lower limit, ranging between 0.27 and 0.45 nmol/min per mg protein (reference: 0.4-1.0), while plasma Lyso-Gb3 levels remained normal (range 0.39 ± 0.33; reference: ≤0.9 ng/mL). For both hemizygous subjects investigated, brain magnetic resonance imaging revealed unspecific white matter lesions. One of these subjects had suffered from severe early-onset stroke, the other showed mild hypertrophic cardiomyopathy.Presence of isolated heterozygous -10C >T SNP is not associated with clinically relevant symptoms or organ manifestations as seen in FD. Respective polymorphisms might, however, play a role in modifying disease severity in FD. Great care has to be taken in respective subjects suspected to suffer from nonclassical FD in order to prevent unnecessary Fabry-specific therapy.

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

Cited by 13 publications

References 24 publications

Significant hearing loss in Fabry disease: Study of the Danish nationwide cohort prior to treatment

Significant hearing loss in Fabry disease: Study of the Danish nationwide cohort prior to treatment

Characterization of vertigo and hearing loss in patients with Fabry disease

Clinical impact of the alpha-galactosidase A gene single nucleotide polymorphism -10C>T

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