Enzyme-replacement therapy in mucopolysaccharidosis I.

Background: Mucopolysaccharidosis I is a lysosomal storage disease caused b y 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. T he patients were evaluated at base line and at 6, 12, 26, and 52 weeks by d etailed clinical examinations, magnetic resonance imaging of the abdomen an d brain, echocardiography, range-of-motion measurements, polysomnography, c linical laboratory evaluations, measurements of leukocyte (alpha)-L-iduroni dase activity, and urinary glycosaminoglycan excretion. Results: Hepatosplenomegaly decreased significantly in all patients, and th e 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 pat ients. The mean maximal range of motion of shoulder flexion and elbow exten sion increased significantly. The number of episodes of apnea and hypopnea during sleep decreased 61 percent. New York Heart Association functional cl ass improved by one or two classes in all patients. Urinary glycosaminoglyc an excretion decreased after three to four weeks of treatment; the mean red uction at 52 weeks was 63 percent of base-line values. Five patients had tr ansient urticaria during infusions. Serum antibodies to (alpha)-L-iduronida se were detected in four patients. Conclusions: In patients with mucopolysaccharidosis I, treatment with recom binant human (alpha)-L-iduronidase reduces lysosomal storage in the liver a nd ameliorates some clinical manifestations of the disease. (N Engl J Med 2 001;344:182-8.) Copyright (C) 2001 Massachusetts Medical Society.