CRIM Responses in Pompe Disease

庞贝氏症（糖原累积病II型; MIM 232300）是一种典型的溶酶体储存疾病 导致婴儿型患者在生命的第一年死亡， 导致心肺衰竭的心肌病。美而赞（阿糖苷酶α，重组人 酸性α-葡糖苷酶/GAA，rhGAA）在2006年4月被批准用于治疗庞贝氏症。的 美而赞ERT的可用性改善了大多数庞贝氏症患者的结果;然而， 一部分婴儿庞贝氏症患者对ERT反应不佳，随后死于心肺功能衰竭。 失败反应不良的庞贝氏症患者通常缺乏残留的GAA表达，并且这些患者的GAA表达水平可能会降低。 患者为交叉反应免疫物质阴性（CRIM阴性）。 本提案的目的是评价这些接受ERT +/-治疗的罕见CRIM阴性庞贝氏症患者 免疫抑制，通过招募他们参加前瞻性/回顾性自然史研究， Lysosomal Disease Network.受试者将从网络入组，并收集关于 临床终点的数量，以确定这种疾病的自然史。入组将包括患者 预测其对当前治疗的临床反应较差。研究对象都是婴儿期的交叉反应 免疫物质（CRIM）阴性庞贝氏症患者的临床方案起始酶 替代疗法（ERT），有或没有免疫抑制。它们将与获得的数据进行比较 婴儿CRIM阳性庞贝氏症患者在相似的年龄开始接受ERT治疗， 方案监测病史和ERT疾病结局。

Pompe disease (Glycogen storage disease type II; MIM 232300) is a classical lysosomal storage disorder that causes death in the first year of life for patients with the infantile form due to a progressive cardiomyopathy leading to cardiorespiratory failure. Myozyme (alglucosidase alpha, recombinant human acid alpha-glucosidase/GAA, rhGAA) was approved in April 2006 as a treatment for Pompe Disease. The availability of ERT with Myozyme has improved the outcome of most patients with Pompe disease; however, a subset of infantile Pompe patients responds poorly to ERT, subsequently dying from cardiorespiratory failure. Poorly-responding Pompe disease patients generally lack residual GAA expression and these patients are cross-reacting immune material-negative (CRIM-negative). The Aims of this proposal would evaluate these rare CRIM-negative Pompe disease patients on ERT +/- immune suppression, by enrolling them in a prospective/retrospective natural history study through the Lysosomal Disease Network. Subjects would be enrolled from the Network and data collected regarding a number of clinical endpoints to determine the natural history of this disorder. Enrollment will include patients for whom a poor clinical response to current therapy is predicted. Patients studied will be all infantile crossreacting immune material (CRIM)-negative Pompe disease patients on a clinical protocol starting enzyme replacement therapy (ERT) with or without immune suppression. They will be compared to data obtained from infantile CRIM-positive Pompe disease patients started on ERT at similar ages and also enrolled in the protocol monitoring history and outcome of the disease on ERT.