Intrathecal enzyme replacement therapy in a patient with mucopolysaccharidosis type I and symptomatic spinal cord compression.
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.
Munoz-Rojas
Maria-Veronica
MV
Hospital de Clinicas de Porto Alegre, Medical Genetics Service, Porto Alegre, Brazil. versonicamunozrojas@msn.com
Vieira
Taiane
T
Costa
Ronaldo
R
Fagondes
Simone
S
John
Angela
A
Jardim
Laura Bannach
LB
Vedolin
Leonardo M
LM
Raymundo
Marcia
M
Dickson
Patricia I
PI
Kakkis
Emil
E
Giugliani
Roberto
R
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
D011994:Recombinant Proteins; D007068:Iduronidase