Enzyme replacement therapy for mucopolysaccharidosis VI from 8 weeks of age-a sibling control study

• Published in: Clinical genetics 2010-05, Vol.77 (5), p.492-498
• Main Authors: McGill, JJ, Inwood, AC, Coman, DJ, Lipke, ML, De Lore, D, Swiedler, SJ, Hopwood, JJ
• Format: Article
• Language: English
• Subjects: Adenylate cyclase; Age; Biological and medical sciences; Carbohydrates (enzymatic deficiencies). Glycogenosis; Case studies; Case-Control Studies; Child, Preschool; Children; Cornea; dose; early intervention; Enzyme Replacement Therapy; Enzymes; Errors of metabolism; Female; Fundamental and applied biological sciences. Psychology; General aspects. Genetic counseling; Genetic disorders; Genetics of eukaryotes. Biological and molecular evolution; Glycosaminoglycans - urine; Heart; Hormone replacement therapy; Humans; Infant; Infant, Newborn; Joints; Lysosomal enzymes; Male; Maroteaux-Lamy syndrome; Medical genetics; Medical sciences; Metabolic diseases; Mobility; Molecular and cellular biology; mucopolysaccharidosis; Mucopolysaccharidosis VI - complications; Mucopolysaccharidosis VI - physiopathology; Mucopolysaccharidosis VI - therapy; Mucopolysaccharidosis VI - urine; N-Acetylgalactosamine-4-Sulfatase - therapeutic use; neonatal period; Pregnancy; Range of Motion, Articular - physiology; Scoliosis; Scoliosis - complications; Siblings
• ISSN: 0009-9163; 1399-0004
• DOI: 10.1111/j.1399-0004.2009.01324.x

McGill JJ, Inwood AC, Coman DJ, Lipke ML, de Lore D, Swiedler SJ, Hopwood JJ. Enzyme replacement therapy for mucopolysaccharidosis VI from 8 weeks of age–a sibling control study Mucopolysaccharidosis type VI (MPS VI) is a progressive, multisystem disorder caused by a deficiency of the lysosomal enzyme N‐acetylgalactosamine‐4‐sulphatase (ASB). Enzyme replacement therapy (ERT) has been shown to clinically benefit affected individuals greater than 6 years of age. This case control study of affected siblings assessed the safety, efficacy and benefits of ERT in children less than 5 years of age. Siblings, aged 8 weeks and 3.6 years, were treated weekly with 1 mg/kg recombinant human N‐acetylgalactosamine‐4‐sulphatase (rhASB) with an end‐point of 3.6 years. Clinical and biochemical parameters were monitored to assess the benefits of ERT. The treatment was well tolerated by both siblings. In the younger sibling, ERT was associated with the absence of the development of scoliosis and preserved joint movement, cardiac valves and facial morphology. The older sibling had a marked improvement in joint mobility and cardiac valve pathology and scoliosis slowed or stabilized. Corneal clouding and progressive skeletal changes were observed despite treatment. This study demonstrated a clear benefit of early initiation of ERT to slow or prevent the development of significant pathological changes of MPS VI. These results indicate that the earlier ERT is started, the greater the response.