Abstract for presentation at 11th International Congress of Human Genetics

CSF GAG behavior during intra-thecal enzyme replacement therapy in a patient with MPS I and spinal cord compression

  • M Verónica Muñoz R, Medical Genetics Service, Hosp Clin P Alegre, Porto Alegre, RS, Brazil, Brazil
  • Taiane Vieira, Medical Genetics Service, Hosp Clin P Alegre, Porto Alegre, RS, Brazil, Brazil
  • Dr Ronaldo Costa, Medical Genetics Service, Hosp Clin P Alegre, Porto Alegre, RS, Brazil, Brazil
  • Ms Leonardo Vedolin, Imaging Service, Mae de Deus Center, Porto Alegre, RS, Brazil, Brazil
  • Ms Simone Canani, Medical Genetics Service, Hosp Clin P Alegre, Porto Alegre, RS, Brazil, Brazil
  • MD, PhD Laura Jardim, Medical Genetics Service, Hosp Clin P Alegre, Porto Alegre, RS, Brazil, Brazil
  • Biol MS Márcia Raymundo, Medical Genetics Service, Hosp Clin P Alegre, Porto Alegre, RS, Brazil, Brazil
  • MD, PhD Roberto Giugliani, Medical Genetics Service, Hosp Clin P Alegre, Porto Alegre, RS, Brazil, Brazil

    • Introduction: In MPS I, deficiency of α-L-iduronidase and subsequent glycosaminoglycan (GAG) storage can cause spinal cord compression in the cervical meninges. Surgical treatment carries a high risk of morbidity and mortality. As intravenous enzyme replacement therapy (ERT) is not likely to cross the blood-brain barrier, we investigated the behavior of GAG storage in CSF during intrathecal recombinant human α-L-iduronidase (IT rhIDU) in an MPS I patient with spinal cord compression. Purpose: To evaluate the behavior of GAG concentration in CSF before and after IT ERT in a MPS I patient with spinal cord compression due to cervical meningeal storage.
    Methods: CSF GAG concentration was assessed at baseline and during 4 IT monthly infusions of rhIDU administered via lumbar puncture (LP) in a MPS I patient. Previous to rhIDU infusion ~9 mL of CFS were retrieved after opening pressure measurement. CSF was also assessed for protein, glucose, and cell count.
    Results: No clinically significant changes on CSF protein, glucose, or cell count were found. CSF GAG results revealed pretreatment values above normal standards: 13.3 mg/L (NV < 12 mg/L). A progressive decrease on following months was observed. After 4 IT rhIDU infusions, CSF GAG values were found within normal limits: 10.3 mg/L. When comparing both results a 22.5% decrease was observed. CNS opening presure was found normal on all LP and presenting a decreasing trend.
    Conclusions: IT rhIDU seems to play an effective role in decreasing the concentration of GAGs in CSF which, in turn, may prevent further GAG storage in meningeal tissues possibly offering a better outcome in neurologic morbidity for this patient. IT rhIDU seems to be an emerging safe new tool to treat spinal cord compression due to GAG storage in MPS I.

    Conference Organiser - ICMS Pty Ltd