title: Enzyme replacement therapy attenuates disease progression in two Japanese siblings with mucopolysaccharidosis type VI.
abstract: Mucopolysaccharidosis type VI (MPS VI) is a progressive, multisystem autosomal recessive lysosomal disorder resulting from deficient N-acetylgalactosamine-4-sulphatase (ASB) and the consequent accumulation of glycosaminoglycan (GAG). Preclinical and clinical studies had demonstrated clinical benefits of early initiation of systemic therapies in patients with MPS. In this case report, two siblings with MPS VI started enzyme replacement therapy (ERT) with weekly infusions of recombinant human ASB (Galsulfase) at 1mg/kg. Sibling 1 started ERT 5.6 years of age and Sibling 2 was 6 weeks old. The disease status in these two siblings prior to and for no less than 36 months of ERT was followed up and compared. The treatment was well tolerated by both siblings. During 36 months of ERT, symptoms typical of MPS VI including short stature, progressive dysmorphic facial features, hepatosplenomegaly, hearing impairment, corneal clouding, and dysostosis multiplex were largely absent in the younger sibling. Her cardiac functions and joint mobility were well preserved. On the other hand, her affected brother had typical MPS VI phenotypic features described above before commencing ERT at the equivalent age, of 3 years. There was significant improvement in the shoulder range of motion and hearing loss after 36 months of treatment and cardiac function was largely preserved. His skeletal deformity and short stature remained unchanged. The results showed that early ERT initiated at newborn is safe and effective in preventing or slowing down disease progression of MPS VI including bone deformities. These observations indicate that early diagnosis and treatment of MPS VI before development of an irreversible disease is critical for optimal clinical outcome.
authors.affiliation: Department of Pediatrics, National Okayama Medical Center, Okayama, Japan.
authors.forename: Mahoko
authors.initials: M
authors.lastname: Furujo
authors.forename: Toshihide
authors.initials: T
authors.lastname: Kubo
authors.forename: Motomichi
authors.initials: M
authors.lastname: Kosuga
authors.forename: Torayuki
authors.initials: T
authors.lastname: Okuyama
mesh_terms: D002675:Child, Preschool; D003241:Consanguinity; D056947:Enzyme Replacement Therapy; D005260:Female; D057238:Growth Charts; D050276:Hand Bones / Q000002:abnormalities / Q000000981:diagnostic imaging; D006720:Homozygote; D006801:Humans; D007564:Japan; D008297:Male; D009085:Mucopolysaccharidosis IV / Q000175:diagnosis* / Q000188:drug therapy* / Q000235:genetics; D020125:Mutation, Missense; D020051:N-Acetylgalactosamine-4-Sulfatase / Q000235:genetics / Q000627:therapeutic use*; D011859:Radiography; D011994:Recombinant Proteins / Q000627:therapeutic use; D013131:Spine / Q000002:abnormalities / Q000000981:diagnostic imaging; D016896:Treatment Outcome; D014574:Uronic Acids / Q000652:urine
chemical_list: D011994:Recombinant Proteins; D014574:Uronic Acids; D020051:N-Acetylgalactosamine-4-Sulfatase; C508864:galsulfase