Inner ear involvement in Fabry disease: Clinical and audiometric evaluation of a large cohort of patients followed in a reference centre

Rodrigues, Jorge; Azevedo, Olga; Sousa, Nuno; Cunha, Damião; Mexedo, Alexandre; Fonseca, Rui

doi:10.1016/j.ejmg.2018.01.006

Cited by 14 publications

(13 citation statements)

References 27 publications

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“…Interestingly, a recent study by Rodrigues and colleagues [25] demonstrated hearing loss at all frequencies in FD patients, indiscriminate of sex in disagreement with the present study. Only one other study by Suntjens and colleagues [6] investigated hearing prior to treatment and found hearing loss at all frequencies at baseline when compared to an otologically healthy control group.…”

Section: Discussioncontrasting

confidence: 99%

“…However, it is worth noting that hearing thresholds were not age and sex corrected in either of these GFR comparisons. In our analysis we found no statistically significant relationship between Z-scores for mGFR and Z-scores for hearing thresholds at all frequencies in PTA 3 , PTA 4 and PTA 6 , in keeping with two studies [5,25]. Yet, in the most recent study [25] an association between albuminuria and hearing loss was detected in contrast to our findings.…”

Section: Discussionsupporting

confidence: 79%

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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: Discussioncontrasting

confidence: 99%

Section: Discussionsupporting

confidence: 79%

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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“…As we previously reported, the p.F113L GLA gene mutation is associated with a high burden of cardiac and CNS manifestations [25,26]. Hearing loss was a common manifestation and age-matched hearing thresholds by frequency are worse in FD than in the general population [18,25,26]. One possible explanation is that the vascular peripheral lesioning could correlate with higher CNS microvascular burden (hearing loss was correlated with microalbuminuria).…”

Section: Discussionmentioning

confidence: 72%

“…FD patients were submitted to a biannual followup, including a systematic multidisciplinary clinical assessment with characterization of the multiorgan involvement by FD [18]. Mainz severity score index (MSSI) was estimated in all patients.…”

Section: Methodsmentioning

confidence: 99%

Parkinson’s Disease and Fabry Disease: Clinical, Biochemical and Neuroimaging Analysis of Three Pedigrees

Gago

Azevedo

Guimarães

et al. 2020

JPD

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“…In a large registry-based study, clinical evidence of cochlear or vestibular dysfunction was present in more than half of the males since 40 years of age, and in more than half of the females after the sixth decade of life 95. Tinnitus and hearing loss may be early symptoms in children with classic FD1,2 and are also more prevalent among patients with later-onset FD variants than in the age-matched general population 97. In most cases, hearing loss is sensorineural and slowly progressive, but the risk of sudden hearing loss is also increased in FD patients.…”

Section: Other Common Later-onset Nondiagnostic Manifestations Of Fdmentioning

confidence: 99%

<p>Multiple phenotypic domains of Fabry disease and their relevance for establishing genotype–phenotype correlations</p>

Oliveira¹,

Ferreira²

2019

TACG

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Fabry disease (FD) is a rare X-linked glycosphingolipidosis resulting from deficient α-galactosidase A (AGAL) activity, caused by pathogenic mutations in the GLA gene. In males, the multisystemic involvement and the severity of tissue injury are critically dependent on the level of AGAL residual enzyme activity (REA) and on the metabolic load of the disease, but organ susceptibility to damage varies widely, with heart appearing as the most vulnerable to storage pathology, even with relatively high REA. The expression of FD can be conceived as a multidomain phenotype, where each of the component domains is the laboratory or clinical expression of the causative GLA mutation along a complex pathophysiologic cascade pathway. The AGAL enzyme activity is the most clinically useful marker of the protein phenotype. The metabolic phenotype and the pathologic phenotype are diverse expressions of the storage pathology, respectively, assessed by biochemical and histological/ultrastructural methods. The storage phenotypes are the direct consequences of enzyme deficiency and hence, together with the enzymatic phenotype, constitute the more specific diagnostic markers of FD. In the pathophysiology cascade, the clinical phenotypes are most distantly linked to the underlying genetic causation, being critically influenced by the patients' gender and age, and modulated by the effects of variation in other genetic loci, of polygenic inheritance and of environmental risk factors. A major challenge in the clinical phenotyping of patients with FD is the differential diagnosis between its nonspecific, later-onset complications, particularly the cerebrovascular, cardiac and renal, and similar chronic illnesses that are common in the general population. Comprehensive phenotyping, whenever possible performed in hemizygous males, is therefore crucial for grading the severity of pathogenic GLA variants, to clarify the phenotypic correlations of hypomorphic alleles, to define benign polymorphisms, as well as to establish the pathogenicity of variants of uncertain significance.

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Inner ear involvement in Fabry disease: Clinical and audiometric evaluation of a large cohort of patients followed in a reference centre

Cited by 14 publications

References 27 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

Parkinson’s Disease and Fabry Disease: Clinical, Biochemical and Neuroimaging Analysis of Three Pedigrees

<p>Multiple phenotypic domains of Fabry disease and their relevance for establishing genotype–phenotype correlations</p>

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Inner ear involvement in Fabry disease: Clinical and audiometric evaluation of a large cohort of patients followed in a reference centre

Cited by 14 publications

References 27 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

Parkinson’s Disease and Fabry Disease: Clinical, Biochemical and Neuroimaging Analysis of Three Pedigrees

<p>Multiple phenotypic domains of Fabry disease and their relevance for establishing genotype&ndash;phenotype correlations</p>

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<p>Multiple phenotypic domains of Fabry disease and their relevance for establishing genotype–phenotype correlations</p>