Intrathecal administration of recombinant human N-acetylgalactosamine 4-sulfatase to a MPS VI patient with pachymeningitis cervicalis.
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.
Muñoz-Rojas
María Verónica
MV
Post Graduation Program in Child and Adolescent Health, UFRGS, Porto Alegre, RS, Brazil.
Horovitz
Dafne Dain Gandelman
DD
Jardim
Laura Bannach
LB
Raymundo
Marcia
M
Llerena
Juan Clinton
JC
de Magalhães
Tatiana de Sá Carneiro Pacheco
Tde S
Vieira
Taiane Alves
TA
Costa
Ronaldo
R
Kakkis
Emil
E
Giugliani
Roberto
R
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
D011994:Recombinant Proteins; D020051:N-Acetylgalactosamine-4-Sulfatase; C508864:galsulfase