Munoz-Rojas Maria-Veronica, Vieira Taiane, Costa Ronaldo, Fagondes Simone, John Angela, Jardim Laura Bannach, Vedolin Leonardo M, Raymundo Marcia, Dickson Patricia I, Kakkis Emil, Giugliani Roberto
Hospital de Clinicas de Porto Alegre, Medical Genetics Service, Porto Alegre, Brazil.
Am J Med Genet A. 2008 Oct 1;146A(19):2538-44. doi: 10.1002/ajmg.a.32294.
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.
在黏多糖贮积症I型中，α-L-艾杜糖醛酸酶缺乏可导致脊髓受压（SCC），原因是糖胺聚糖（GAGs）在颈段脑膜内蓄积。由于静脉内酶替代疗法（ERT）不太可能使酶透过血脑屏障，因此针对该并发症的标准治疗通常是手术治疗，而手术具有较高的发病率和死亡率风险。我们报告了在一名患有SCC且拒绝手术治疗的黏多糖贮积症I型患者中使用鞘内注射（IT）拉罗尼酶的情况。在基线时进行了评估，包括临床和生化评估、四肢体感诱发电位、12分钟步行试验以及中枢神经系统的MRI研究。通过腰椎穿刺每月进行4次IT注射拉罗尼酶后，评估这些参数的变化。据我们所知，这是首例接受IT ERT的黏多糖贮积症患者。未观察到重大不良事件。血清化学指标无临床显著变化。脑脊液GAG结果显示，治疗前值略高于正常标准：13.3mg/L（正常范围<12mg/L），IT注射拉罗尼酶后处于正常水平（10.3mg/L）。12分钟步行试验显示改善了14%，在稳定性和步态控制方面表现更好。最大自主通气量相对于预测值提高了55.6%（基线时为26.7%，相比之下为41.9%）；最大吸气压力相对于预测值提高了36.6%（基线时为26.8%，变为36.7%）；肺弥散相对于预测值提高了17.6%。总之，尽管该例患者使用IT拉罗尼酶观察到的改善情况应在更多患者中得到证实，但该方法似乎是黏多糖贮积症I型中SCC的一种安全治疗方法。
