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. 2010 Apr;30(2):87-93.

Inner ear involvement in Anderson-Fabry disease: long-term follow-up during enzyme replacement therapy

B Sergi  1 , G Conti, G Paludetti; Interdisciplinary Study Group On Fabry Disease
Affiliations

Inner ear involvement in Anderson-Fabry disease: long-term follow-up during enzyme replacement therapy

B Sergi et al. Acta Otorhinolaryngol Ital. 2010 Apr.

Abstract
in English, Italian

This study aimed to evaluate audiological and vestibular involvement in Fabry disease and the effects of enzyme replacement therapy with human alpha-galactosidase A. The study population comprised 20 patients (11 males, 9 females) aged 15-69 years (mean 39.7). Patients underwent a complete clinical and instrumental evaluation before starting and during enzyme replacement therapy. Median follow-up was 51.5 months (range 25-73). Nine patients (45%) complained of hearing symptoms (hearing loss, tinnitus); for six of them the onset and/or progression of the hearing loss were sudden. Vertigo or dizziness was reported by 6 patients (30%). Audiological evaluation showed a sensorineural hearing loss in 18 ears (45%; 10 in male patients, 8 in females). The hearing thresholds for 0.5, 1, 2 and 4 kHz frequencies ranged from 10 to 65 dB HL. Hearing loss was unilateral in 8 cases (40%; 4 in male patients, 4 in females). Also high frequency hearing loss for 4 and 8 kHz was evaluated. No signs of retro-cochlear lesions were observed by means of otoacoustic emissions and auditory brainstem response. Vestibular examinations showed a functional impairment in 7 ears (17.5%, all male patients). During enzyme replacement therapy the auditory function showed some degrees of worsening but no significant changes were observed at statistical analysis. In conclusion involvement of the inner ear is common in men and women with Fabry disease. In this study, a high incidence of cochlear hearing loss was found, which was typically unilateral and showed onset and/or progression by sudden episodes. Vascular or hydropic mechanisms could be hypothesized to explain audiological findings. Vestibular involvement showed a lower incidence and different pattern, thus suggesting that several patho-physiological mechanisms could play a role in determining inner ear damage in Fabry disease. Results obtained show that enzyme replacement therapy may stabilize hearing function; however, further studies on the physiopathology of the inner ear damage are needed.

Questo studio valuta le manifestazioni audio-vestibolari della malattia di Fabry e gli effetti a lungo termine della terapia sostitutiva con l’enzima ricombinate α-galactosidasi A. Un gruppo di 20 pazienti (11 uomini, 9 donne) di età compresa tra 15 e 69 anni (media 39,7) è stato sottoposto a una completa valutazione clinico-strumentale audio-vestibolare prima dell’inizio e durante la terapia con l’enzima. Il follow-up medio è stato di 51,5 mesi (range: 25-73). Nove pazienti (45%) riferivano sintomi audiologici (ipoacusia, acufeni) e per 6 di loro l’insorgenza e la progressione dell’ipoacusia è stata improvvisa. Sei pazienti (30%) lamentavano vertigine e instabilità. I test audiometrici hanno evidenziato la presenza di una ipoacusia neurosensoriale in 18 orecchi (45%; 10 in uomini, 8 in donne). La soglia uditiva per le frequenze 0,5,-4 kHz era compresa tra 10 e 65 dB HL. Abbiamo inoltre valutato l’ipoacusia per le frequenze acute (4-8 kHz). L’ipoacusia era monolaterale in 8 casi (40%; 4 in uomini, 4 in donne). Le otoemissioni acustiche e i potenziali uditivi del tronco hanno escluso lesioni retrococleari. La valutazione vestibolare ha evidenziato un deficit labirintico in 7 orecchi (17,5%, tutti uomini). Durante la terapia sostitutiva, un lieve ma non significativo peggioramento della funzionalità uditiva è stato osservato. In conclusione l’interessamento dell’orecchio interno è comune nei pazienti sia maschili che femminili con la malattia di Fabry. La nostra casistica ha evidenziato una alta indicenza di ipoacusia neurosensoriale cocleare, tipicamente monolaterale e a insorgenza/progressione improvvisa, portando ad ipotizzare una genesi idropica o vascolare come causa di questi sintomi. I deficit vestibolari sono meno frequenti. I nostri risultati dimostrano come la terapia sostitutiva possa evitare la progressione della malattia a livello dell’orecchio interno.

Keywords: Enzyme replacement therapy; Fabry disease; Inner ear; Sensorineural hearing loss; Vestibular damage; α-galactosidase A.

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Figures

Fig. 1
Fig. 1
Audiometric curve with median values for each frequency.
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