title: Intrathecal administration of recombinant human N-acetylgalactosamine 4-sulfatase to a MPS VI patient with pachymeningitis cervicalis.
abstract: In mucopolysaccharidosis VI, or Maroteaux-Lamy syndrome, deficiency of N-acetylgalactosamine 4-sulfatase leads to storage of glycosaminoglycans (GAGs) and MPS VI patients often develop spinal cord compression during the course of the disease due to GAG storage within the cervical meninges, requiring neurosurgical intervention, as intravenous (IV) enzyme replacement therapy (ERT) is not expected to cross the blood-brain barrier. We report the use of intrathecal (IT) recombinant human N-acetylgalactosamine 4-sulfatase (arylsulfatase B, or ASB) in a MPS VI child with spinal cord compression whose parents initially refused the surgical treatment. Assessments were performed at baseline, with clinical, neurological and biochemical evaluations, urodynamic studies and MRI of the CNS. Changes on these parameters were evaluated after IT infusions of ASB administered monthly via lumbar puncture (LP) in a IV ERT naive patient. To our knowledge, this was the first MPS VI patient who received IT ERT. Despite significant urodynamic improvement and some neurological amelioration, the patient developed worsening of walking capacity. After IV ERT was started, the patient presented with a generalized hypotonia and a life-saving surgical fixation of the neck was then performed. The results observed on this MPS VI patient suggest that instability of the cervical vertebrae could be unmasked by IV ERT as joint storage is reduced, and the decrease in neck stiffness and stability could confound the expected improvement of SCC manifestations following IT ERT. The study of further patients, if possible in a clinical trial setting, is needed to evaluate the potential of a non-surgical IT ERT treatment of SCC for MPS VI.
authors.affiliation: Post Graduation Program in Child and Adolescent Health, UFRGS, Porto Alegre, RS, Brazil.
authors.forename: María Verónica
authors.initials: MV
authors.lastname: Muñoz-Rojas
authors.forename: Dafne Dain Gandelman
authors.initials: DD
authors.lastname: Horovitz
authors.forename: Laura Bannach
authors.initials: LB
authors.lastname: Jardim
authors.forename: Marcia
authors.initials: M
authors.lastname: Raymundo
authors.forename: Juan Clinton
authors.initials: JC
authors.lastname: Llerena
authors.forename: Tatiana de Sá Carneiro Pacheco
authors.initials: Tde S
authors.lastname: de Magalhães
authors.forename: Taiane Alves
authors.initials: TA
authors.lastname: Vieira
authors.forename: Ronaldo
authors.initials: R
authors.lastname: Costa
authors.forename: Emil
authors.initials: E
authors.lastname: Kakkis
authors.forename: Roberto
authors.initials: R
authors.lastname: Giugliani
mesh_terms: D002648:Child; D006801:Humans; D007278:Injections, Spinal; D008297:Male; D008581:Meningitis / Q000150:complications*; D009087:Mucopolysaccharidosis VI / Q000188:drug therapy*; D020051:N-Acetylgalactosamine-4-Sulfatase / Q000008:administration & dosage*; D011994:Recombinant Proteins / Q000008:administration & dosage; D013117:Spinal Cord Compression
chemical_list: D011994:Recombinant Proteins; D020051:N-Acetylgalactosamine-4-Sulfatase; C508864:galsulfase