Enzyme-replacement therapy in mucopolysaccharidosis I.
Enzyme-replacement therapy in mucopolysaccharidosis I.
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DOI：
10.1056/nejm200101183440304
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发表时间：
2001-01-18
影响因子：
158.5
通讯作者：
Thompson, JN
中科院分区：
文献类型：
--
作者：
Kakkis, ED;Muenzer, J;Thompson, JN
背景：粘多糖病I是一种因α-L-艾杜糖苷酶缺陷引起的溶酶体贮积性疾病。方法：用重组人(α)-L-艾杜糖酸酶治疗粘多糖病I期患者10例，年龄5~22岁，每公斤体重125,000 U，每周1次，疗程52周。通过详细的临床检查、腹部和脑的磁共振成像、超声心动图、活动度测量、多导睡眠图、临床实验室检查、白细胞(α)-L-艾杜糖醛酸酶活性测定和尿糖胺多糖排泄，在基线和6、12、26、52周对患者进行评估。结果：所有患者的肝脾肿大均明显缩小，其中8例患者26周时肝脏大小与体重和年龄相一致。在6名青春期前患者中，身高和体重的增长率在52周时分别平均增加了85%和131%。肩前屈、伸肘的平均最大活动度明显增加。睡眠中呼吸暂停和低呼吸发作的次数减少了61%。纽约心脏协会功能分级在所有患者中都改善了一到两级。治疗3至4周后，尿糖胺聚糖排泄量减少；52周时平均减少63%。5名患者在输液过程中出现一过性荨麻疹。4例患者检测血清抗(α)-L艾杜糖苷酶抗体。结论：重组人(α)-L艾杜糖酸酶治疗粘多糖病I型，减少了溶酶体在肝脏中的蓄积，改善了部分临床表现。(《英国医学杂志》2001；344：182-8)版权所有(C)2001年马萨诸塞州医学会。
Background: Mucopolysaccharidosis I is a lysosomal storage disease caused by a deficiency of the enzyme (alpha)-L-iduronidase. We evaluated the effect of enzyme-replacement therapy with recombinant human (alpha)-L-iduronidase in patients with this disorder.Methods: We treated 10 patients with mucopolysaccharidosis I (age, 5 to 22 years) with recombinant human (alpha)-L-iduronidase at a dose of 125,000 U per kilogram of body weight given intravenously once weekly for 52 weeks. The patients were evaluated at base line and at 6, 12, 26, and 52 weeks by detailed clinical examinations, magnetic resonance imaging of the abdomen and brain, echocardiography, range-of-motion measurements, polysomnography, clinical laboratory evaluations, measurements of leukocyte (alpha)-L-iduronidase activity, and urinary glycosaminoglycan excretion.Results: Hepatosplenomegaly decreased significantly in all patients, and the size of the liver was normal for body weight and age in eight patients by 26 weeks. The rate of growth in height and weight had increased by a mean of 85 and 131 percent, respectively, at 52 weeks in the six prepubertal patients. The mean maximal range of motion of shoulder flexion and elbow extension increased significantly. The number of episodes of apnea and hypopnea during sleep decreased 61 percent. New York Heart Association functional class improved by one or two classes in all patients. Urinary glycosaminoglycan excretion decreased after three to four weeks of treatment; the mean reduction at 52 weeks was 63 percent of base-line values. Five patients had transient urticaria during infusions. Serum antibodies to (alpha)-L-iduronidase were detected in four patients.Conclusions: In patients with mucopolysaccharidosis I, treatment with recombinant human (alpha)-L-iduronidase reduces lysosomal storage in the liver and ameliorates some clinical manifestations of the disease. (N Engl J Med 2001;344:182-8.) Copyright (C) 2001 Massachusetts Medical Society.