Hajioff D, Enever Y, Quiney R, Zuckerman J, Mackermot K, Mehta A
Department of Otolaryngology, Royal Free Hospital, Pond Street, London NW3 2QG, UK.
J Inherit Metab Dis. 2003;26(8):787-94. doi: 10.1023/B:BOLI.0000009948.86528.72.
The aim of this study was to describe the nature and prevalence of hearing loss in Fabry disease (McKusick 301500), a rare X-linked lysosomal storage disorder, and its response to enzyme replacement therapy with agalsidase alfa. Fifteen hemizygous male Fabry patients (aged 25-49 years) were randomized to receive placebo or enzyme replacement therapy for 6 months; all have received open-label enzyme replacement therapy for an additional 24 months thus far. Pure-tone audiometry, impedance audiometry and otoacoustic emission testing were performed at 0 (baseline), 6, 18 and 30 months. Four patients (27%) had bilateral and 7 (47%) had unilateral high-frequency sensorineural hearing loss (SNHL). Two (13%) had unilateral middle ear effusions with conductive losses persisting beyond 6 months. Only 3 (20%) had normal hearing. High-frequency SNHL deteriorated over the first 6 months in both placebo and active treatment groups by a median 4.3 dB ( p =0.002, Wilcoxon matched pairs). This hearing loss subsequently improved above baseline by 2.1 dB at 18 months ( p =0.02) and by 4.9 dB at 30 months ( p =0.004). In conclusion, significant hearing loss, usually high-frequency SNHL, is a common manifestation of Fabry disease in adults. alpha-Galactosidase A replacement therapy with agalsidase alfa appears to reverse the hearing deterioration in these patients. This improvement is gradual, however, suggesting the need for long-term enzyme replacement therapy.
本研究的目的是描述法布里病（麦库西克301500）——一种罕见的X连锁溶酶体贮积症——听力损失的性质和患病率，以及其对阿加糖酶α酶替代疗法的反应。15名半合子男性法布里病患者（年龄25 - 49岁）被随机分组，接受安慰剂或酶替代疗法6个月；到目前为止，所有人均已接受开放标签的酶替代疗法额外24个月。在0（基线）、6、18和30个月时进行纯音听力测定、声阻抗测听和耳声发射测试。4名患者（27%）有双侧听力损失，7名（47%）有单侧高频感音神经性听力损失（SNHL）。2名（13%）有单侧中耳积液，传导性听力损失持续超过6个月。只有3名（20%）听力正常。在安慰剂组和积极治疗组中，高频SNHL在最初6个月均恶化，中位数为4.3 dB（p = 0.002，威尔科克森配对检验）。这种听力损失随后在18个月时改善至基线以上2.1 dB（p = 0.02），在30个月时改善至基线以上4.9 dB（p = 0.004）。总之，显著的听力损失，通常为高频SNHL，是法布里病在成人中的常见表现。用阿加糖酶α进行的α - 半乳糖苷酶A替代疗法似乎能逆转这些患者的听力恶化。然而，这种改善是渐进的，提示需要长期的酶替代疗法。
