Hearing loss in adult patients with Fabry disease treated with enzyme replacement therapy.
BACKGROUND
Data on prevalence, natural history, and effect of enzyme replacement therapy (ERT) on hearing loss (HL) in Fabry disease (FD) are scarce.


METHODS
This is a retrospective study with cross-sectional and longitudinal analyses. Low and high-frequency HL in the Dutch FD cohort was studied in four groups: classical and non-classical FD patients with or without ERT. To study effects of ERT, longitudinal data, corrected for age and gender according to ISO-1999 guidelines, were analyzed with mixed models.


RESULTS
In the cross-sectional analysis, 107 FD patients (41 males), median age 47.6 years (18.8-80.6) were analyzed. At baseline, i.e., before start of ERT, HL was present in 18 patients (16.8 %), of whom four had bilateral sensorineural HL. HL was more often present in patients with the classical phenotype than non-classical patients (p < 0.01). Likewise, males had more often HL than females. Compared to the general population, FD patients show a median HL of 8.2 dB at low frequencies (p < 0.01) and 29.5 dB at ultra-high frequencies (p < 0.01). Longitudinal analyses (n = 91) revealed that ERT treated patients show a similar rate of decline, not significantly different from healthy controls.


CONCLUSIONS
Adult FD patients, especially classical affected males, show impaired hearing. Longitudinal analyses during ERT in these patients demonstrates a decline of HL similar to healthy controls, but HL present before initiation of therapy cannot be reversed. Whether early therapy can prevent hearing loss is unknown.
Sphinx-Amsterdam Lysosome Center, Department of Endocrinology and metabolism, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Eefje B
EB
Suntjens
Bouwien E
BE
Smid
Marieke
M
Biegstraaten
Wouter A
WA
Dreschler
Carla E M
CE
Hollak
Gabor E
GE
Linthorst
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001301:Audiometry, Pure-Tone; D001309:Auditory Threshold; D003430:Cross-Sectional Studies; D018450:Disease Progression; D056947:Enzyme Replacement Therapy; D000795:Fabry Disease / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D005260:Female; D006312:Hearing Loss, Bilateral / Q000175:diagnosis / Q000209:etiology* / Q000523:psychology; D006319:Hearing Loss, Sensorineural / Q000175:diagnosis / Q000209:etiology* / Q000523:psychology; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D012189:Retrospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index; D012737:Sex Factors; D016896:Treatment Outcome; D055815:Young Adult; D000519:alpha-Galactosidase / Q000235:genetics / Q000627:therapeutic use*
C576330:GLA protein, human; D000519:alpha-Galactosidase