title: Intrathecal enzyme replacement therapy in a patient with mucopolysaccharidosis type I and symptomatic spinal cord compression.
abstract: In mucopolysaccharidosis I, deficiency of alpha-L-iduronidase can cause spinal cord compression (SCC) due to storage of glycosaminoglycans (GAGs) within the cervical meninges. As intravenous enzyme replacement therapy (ERT) is not likely to provide enzyme across the blood-brain barrier, standard treatment for this complication is usually surgical, which has a high morbidity and mortality risk. We report on the use of intrathecal (IT) laronidase in a MPS I patient with SCC who refused the surgical treatment. Assessments were performed at baseline, with clinical and biochemical evaluations, 4-extremity somatosensory evoked potentials, 12 min walk test and MRI studies of the CNS. Changes on these parameters were evaluated after 4 IT infusions of laronidase administered monthly via lumbar puncture. To our knowledge, this was the first MPS patient who received IT ERT. No major adverse events were observed. There were no clinically significant changes in serum chemistries. CSF GAG results revealed pretreatment values slightly above normal standards: 13.3 mg/L (NV < 12 mg/L) which after IT laronidase infusions were within normal levels (10.3 mg/L). 12MWT presented a 14% improvement, with better performance on stability and gait control. Maximum voluntary ventilation showed 55.6% improvement considering the percentage of predicted (26.7% at baseline compared to 41.9%); Maximum Inspiration Pressure improved 36.6% of predicted (26.8% at baseline to 36.7%); Pulmonary diffusion improved 17.6% of predicted %. In conclusion, although the improvement observed in this case with IT laronidase should be confirmed in further patients, this procedure seems to be a safe treatment for SCC in MPS I.
authors.affiliation: Hospital de Clinicas de Porto Alegre, Medical Genetics Service, Porto Alegre, Brazil. versonicamunozrojas@msn.com
authors.forename: Maria-Veronica
authors.initials: MV
authors.lastname: Munoz-Rojas
authors.forename: Taiane
authors.initials: T
authors.lastname: Vieira
authors.forename: Ronaldo
authors.initials: R
authors.lastname: Costa
authors.forename: Simone
authors.initials: S
authors.lastname: Fagondes
authors.forename: Angela
authors.initials: A
authors.lastname: John
authors.forename: Laura Bannach
authors.initials: LB
authors.lastname: Jardim
authors.forename: Leonardo M
authors.initials: LM
authors.lastname: Vedolin
authors.forename: Marcia
authors.initials: M
authors.lastname: Raymundo
authors.forename: Patricia I
authors.initials: PI
authors.lastname: Dickson
authors.forename: Emil
authors.initials: E
authors.lastname: Kakkis
authors.forename: Roberto
authors.initials: R
authors.lastname: Giugliani
mesh_terms: D000328:Adult; D004334:Drug Administration Schedule; D006801:Humans; D007068:Iduronidase / Q000008:administration & dosage* / Q000235:genetics / Q000627:therapeutic use; D007278:Injections, Spinal / Q000009:adverse effects / Q000379:methods; D008297:Male; D008059:Mucopolysaccharidosis I / Q000150:complications* / Q000628:therapy*; D011859:Radiography; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D013117:Spinal Cord Compression / Q000150:complications* / Q000000981:diagnostic imaging / Q000628:therapy*; D013129:Spinal Puncture / Q000379:methods; D016896:Treatment Outcome
chemical_list: D011994:Recombinant Proteins; D007068:Iduronidase