The impact of laronidase treatment in otolaryngological manifestations of patients with mucopolysaccharidosis

ABSTRACT INTRODUCTION: Mucopolysaccharidosis (MPS) is a lysosomal storage disease caused by deficiency of a-l-iduronidase. The otolaryngological findings include hearing loss, otorrhea, recurrent otitis, hypertrophy of tonsils and adenoid, recurrent rhinosinusitis, speech disorders, snoring, oral breathing and nasal obstruction. OBJECTIVE: To evaluate the impact of enzymatic replacement therapy with laronidase (Aldurazyme(r)) in patients with mucopolysaccharidosis (MPS I), regarding sleep and hearing disorders, and clinical manifestations in the upper respiratory tract (URT). METHODS: Nine patients with MPS I (8 Hurler-Scheie, and 1 Scheie phenotypes) of both sexes, ages ranging between 3 and 20 years, were included in this study. Patients were evaluated between seven and 11 months before the treatment and between 16 and 22 months after the onset of the enzymatic replacement. They were all submitted to a clinical and otolaryngological evaluation, including nasofibroscopical, polysomnographic and audiologic exams. RESULTS: The results' data showed decreasing of the frequency of ear, nose and throat infections, with improvement of the rhinorrhea and respiratory quality. No remarkable changes were observed regarding macroglossia and tonsil and adenoid hypertrophy. Audiometric and polysomnographic evaluations did not show statistical significance. CONCLUSION: Enzymatic replacement therapy in patients with mucopolysaccharidosis I provides control of recurrent URT infections, rhinorrhea and respiratory quality, however it is does not seem to improve audiologic and polisomnographic parameters, with no effect on adenoid and tonsils hypertrophy and macroglossia.引言：黏多糖贮积症（Mucopolysaccharidosis, MPS）是一种因α-L-艾杜糖醛酸酶缺乏引发的溶酶体贮积症。其耳鼻咽喉科表现包括听力损失、耳漏、复发性中耳炎、扁桃体及腺样体肥大、复发性鼻-鼻窦炎、言语障碍、打鼾、张口呼吸与鼻阻塞。 研究目的：评估拉罗尼酶（laronidase，商品名Aldurazyme®）酶替代疗法对Ⅰ型黏多糖贮积症（MPS I）患者睡眠与听力障碍，以及上呼吸道（upper respiratory tract, URT）临床表现的影响。 研究方法：本研究纳入9例MPS I患者，其中8例为Hurler-Scheie表型，1例为Scheie表型，男女均有，年龄介于3~20岁。分别于酶替代治疗启动前7~11个月，以及治疗启动后16~22个月对患者开展评估。所有受试者均接受临床及耳鼻咽喉科评估，包括鼻纤维内镜检查、多导睡眠监测及听力学检查。 研究结果：结果数据显示，耳、鼻、咽喉感染的发作频率降低，流涕及呼吸质量得到改善。未观察到巨舌症以及扁桃体、腺样体肥大出现显著变化。听力学及多导睡眠监测评估未显示统计学差异。 研究结论：对Ⅰ型黏多糖贮积症患者实施酶替代疗法，可控制复发性上呼吸道感染、流涕及呼吸质量，但似乎无法改善听力学及多导睡眠监测参数，对扁桃体、腺样体肥大及巨舌症无显著疗效。