TY - JOUR

T1 - Hearing loss in fabry disease

T2 - A 16 year follow-up study of the Danish nationwide cohort

AU - Yazdanfard, Puriya Daniel Würtz

AU - Effraimidis, Grigoris

AU - Madsen, Christoffer Valdorff

AU - Nielsen, Lars Holme

AU - Rasmussen, Åse Krogh

AU - Petersen, Jørgen Holm

AU - Sørensen, Søren Schwartz

AU - Køber, Lars

AU - de Abreu, Vitor Hugo Fraga

AU - Larsen, Vibeke Andrée

AU - Feldt-Rasmussen, Ulla

N1 - Publisher Copyright: © 2022

PY - 2022

Y1 - 2022

N2 - Background: Fabry disease (FD) is a lysosomal storage disorder resulting in systemic accumulation of globotriaosylceramide (Gb3) causing multi-organ dysfunction. The audiologic involvement in FD has been neglected in previous studies; while not a lethal aspect of the disease, hearing loss can have a significantly negative impact on quality of life. Objective: To investigate hearing loss from baseline through 16 years follow-up of the Danish FD cohort and to compare audiometric data to other clinical variables. Methods: Data was collected prospectively and assessed retrospectively during a period of 16 years from 83 patients (age: 9–72 years; sex: 29 males and 54 females). 55 patients underwent treatment. Air conduction thresholds was assessed at six frequencies between 0.25 and 8 kHz bilaterally. Data was analyzed using multilinear models. Results: Mean follow-up period for patients undergoing a FD specific treatment was 7.8 years (0–12.8 years, SD 3.8 years, n = 55). Hearing thresholds for FD patients deviated from healthy individuals at all frequencies for both sexes (p < 0.001). Males had more profound hearing loss than females at high frequencies (4,8 kHz) (p = 0.025). There was no improvement in hearing with treatment (p = 0.343♂, p = 0.256♀). No associations between hearing loss and measured glomerular filtration rate, left ventricular wall thickness or cerebral white matter lesions were found. Lower plasma Gb3 concentration correlated with better hearing (p = 0.046) in males. Conclusion: Our findings demonstrated significant hearing loss in FD patients compared to audiologically healthy individuals at all frequencies, and no change in hearing during treatment. Lower plasma Gb3 concentrations correlated with better hearing in males.

AB - Background: Fabry disease (FD) is a lysosomal storage disorder resulting in systemic accumulation of globotriaosylceramide (Gb3) causing multi-organ dysfunction. The audiologic involvement in FD has been neglected in previous studies; while not a lethal aspect of the disease, hearing loss can have a significantly negative impact on quality of life. Objective: To investigate hearing loss from baseline through 16 years follow-up of the Danish FD cohort and to compare audiometric data to other clinical variables. Methods: Data was collected prospectively and assessed retrospectively during a period of 16 years from 83 patients (age: 9–72 years; sex: 29 males and 54 females). 55 patients underwent treatment. Air conduction thresholds was assessed at six frequencies between 0.25 and 8 kHz bilaterally. Data was analyzed using multilinear models. Results: Mean follow-up period for patients undergoing a FD specific treatment was 7.8 years (0–12.8 years, SD 3.8 years, n = 55). Hearing thresholds for FD patients deviated from healthy individuals at all frequencies for both sexes (p < 0.001). Males had more profound hearing loss than females at high frequencies (4,8 kHz) (p = 0.025). There was no improvement in hearing with treatment (p = 0.343♂, p = 0.256♀). No associations between hearing loss and measured glomerular filtration rate, left ventricular wall thickness or cerebral white matter lesions were found. Lower plasma Gb3 concentration correlated with better hearing (p = 0.046) in males. Conclusion: Our findings demonstrated significant hearing loss in FD patients compared to audiologically healthy individuals at all frequencies, and no change in hearing during treatment. Lower plasma Gb3 concentrations correlated with better hearing in males.

KW - Albuminuria

KW - Cardiac dysfunction

KW - Chronic kidney disease

KW - Fabry disease

KW - Genetic disorder

KW - Hearing loss

KW - Lysosomal storage disorder

KW - White matter lesions

KW - X-linked disorder

U2 - 10.1016/j.ymgmr.2022.100841

DO - 10.1016/j.ymgmr.2022.100841

M3 - Journal article

C2 - 35242579

AN - SCOPUS:85124505132

VL - 31

JO - Molecular Genetics and Metabolism Reports

JF - Molecular Genetics and Metabolism Reports

SN - 2214-4269

M1 - 100841

ER -