Enzyme-replacement therapy in mucopolysaccharidosis I.

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.