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Previous Volume 344:182-188 January 18, 2001 Number 3 Next

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ABSTRACT

Background Mucopolysaccharidosis I is a lysosomal storage disease caused by a deficiency of the enzyme -L-iduronidase. We evaluated the effect of enzyme-replacement therapy with recombinant human -L-iduronidase in patients with this disorder.

Methods We treated 10 patients with mucopolysaccharidosis I (age, 5 to 22 years) with recombinant human -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 -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 -L-iduronidase were detected in four patients.

Conclusions In patients with mucopolysaccharidosis I, treatment with recombinant human -L-iduronidase reduces lysosomal storage in the liver and ameliorates some clinical manifestations of the disease.

Source Information

From the Department of Pediatrics, Division of Medical Genetics, Harbor–UCLA Medical Center, Torrance, Calif. (E.D.K., M.P., B.I., J.P., R.D., I.W., R.H.); BioMarin Pharmaceutical, Novato, Calif. (E.D.K.); the University of North Carolina, Chapel Hill, Chapel Hill (J.M.); Vanderbilt University Medical Center, Nashville (G.E.T.); the University of Texas Southwestern Medical Center, Dallas (L.W.); Baylor College of Medicine, Houston (J.B.); and the Department of Biological Chemistry, UCLA School of Medicine, Los Angeles (E.F.N.). Other authors were Kian Ti Yu, M.D., Susie Okazaki, Dave Lewis, M.D., and Ralph Lachman, M.D. (Harbor–UCLA Medical Center, Torrance, Calif.); and Jerry N. Thompson, Ph.D. (University of Alabama at Birmingham, Birmingham).

Address reprint requests to Dr. Kakkis at BioMarin Pharmaceutical, Inc., 371 Bel Marin Keys Blvd., Suite 210, Novato, CA 94949, or at ekakkis{at}biomarinpharm.com.

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